Genetic Markers for Assessing Risk of Developing Schizophrenia

ABSTRACT

This document provides methods and materials related to genetic markers of schizophrenia (SZ). For example, this document provides methods for using such genetic markers to assess risk of developing schizophrenia.

CLAIM OF PRIORITY

This application is a continuation of International Patent ApplicationSerial No. PCT/US2009/058487, filed Sep. 25, 2009, which claims thebenefit of U.S. Provisional Application Ser. No. 61/100,176, filed onSep. 25, 2008, which are incorporated by reference in their entiretyherein.

FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

The U.S. Government has certain rights in this invention pursuant toGrant Nos. R43 MH078437, N01 MH900001, and MH074027, awarded by theNational Institutes of Health.

TECHNICAL FIELD

This invention relates to genetic markers of schizophrenia (SZ). Forexample, methods of using such genetic markers for assessing risk ofdeveloping SZ are provided.

BACKGROUND

The schizophrenia spectrum disorders include schizophrenia (SZ),schizotypal personality disorder (SPD), and/or schizoaffective disorder(SD). Schizophrenia (SZ) is considered a clinical syndrome, and isprobably a constellation of several pathologies. Substantialheterogeneity is seen between cases, which is thought to reflectmultiple overlapping etiologic factors, including both genetic andenvironmental contributions. SD is characterized by the presence ofaffective (depressive or manic) symptoms and schizophrenic symptomswithin the same, uninterrupted episode of illness. SPD is characterizedby a pervasive pattern of social and interpersonal deficits marked byacute discomfort with, and reduced capacity for, close relationships aswell as by cognitive or perceptual distortions and eccentricities ofbehavior, beginning by early adulthood and present in a variety ofcontexts.

Various genes and chromosomes have been implicated in etiology of SZ.Many studies have suggested the presence of one or more important genesrelating to SZ on most or all of the autosomes (Williams et al., Hum.Mol. Genet. 8:1729-1739 (1999); Fallin et al., Am. J. Hum. Genet.77:918-936 (2005); ; Badner et al., Mol. Psychiatry. 7:405-411 (2002);Cooper-Casey et al., Mol. Psychiatry. 10:651-656 (2005); Devlin et al.,Mol. Psychiatry. 7:689-694 (2002); Fallin et al., Am. J. Hum. Genet.73:601-611 (2003); Jablensky, Mol. Psychiatry. 11: 815-836 (2006); Kirovet al., J. Clin. Invest. 115:1440-1448 (2005); Norton et al., Curr.Opin. Psychiatry 19:158-164 (2006); Owen et al., Mol. Psychiatry.9:14-27 (2004)). However, none of these prior studies have used highresolution genetic association methods to systematically compare genesinvolved in SZ. Neither have any of these studies demonstrated thatgenetic polymorphisms in the genes defined herein are important, inparticular in the genetic etiology of SZ.

Due to the severity of these disorders, especially the negative impactof a psychotic episode on a patient, and the diminishing recovery aftereach psychotic episode, there is a need to more conclusively identifyindividuals who have or are at risk of developing schizophrenia (SZ),schizotypal personality disorder (SPD), or schizoaffective disorder(SD), for example, to confirm clinical diagnoses, to allow forprophylactic therapies, to determine appropriate therapies based ontheir genotypic subtype, and to provide genetic counseling forprospective parents with a history of the disorder.

SUMMARY

This disclosure provides methods for determining a subject's risk ofdeveloping schizophrenia based on detecting variations in genes involvedin a number of pathways including: glutamate signaling and metabolism,cell adhesion, cytoskeletal architecture, vesicle formation, andtrafficking, G-protein coupled receptors, carrier proteins andtransporters, cell cycle modulators, neuronal development,calcium/calmodulin signaling, neuropeptide signaling, and severaladditional genes identified by virtue of their interaction with genes inhigh impact pathways and their expression in the central nervous system.This disclosure also provides methods and materials relating todetermining the genetic risk of developing an SSD (e.g., SZ). Forexample, the allelic and genotypic variants identified as describedherein can be used for assessing genetic risk. Specifically, theinvention includes methods for assessing genetic risk based onevaluation of 1025 exemplary SNPs relating to SZ risk. Additionally, thespecific SNPs can be used to capture copy number variation related to SZrisk. The allelic and genotypic variants thus identified can be used forassessing genetic risk.

In one aspect, this document features methods for determining risk ofdeveloping schizophrenia (SZ) in a human subject. Methods can includedetermining the identity of at least one allele of a single nucleotidepolymorphism (SNP) listed in Table 1 (e.g., at nucleotide 31 of SEQ IDNO:656, 665, 248, 639, 25, 494, 700, or 691); and comparing the identityof the allele in the subject with a reference allele, wherein thereference allele is associated with a known risk of developing SZ; andwherein the presence of an allele in the subject that is the same as thereference allele that is associated with the known risk of developing SZindicates the risk that the subject will develop SZ.

In another aspect, this document features methods for determining riskof developing SZ in a human subject. Methods can include: determiningthe copy number of at least one single nucleotide polymorphism (SNP)listed in Table 2 (e.g, at nucleotide 31 of SEQ ID NO:665, 314, 679,597, 523, 619, 402) or Table 3 (e.g., at nucleotide 31 of SEQ ID NO:677,586, 558, 664, 87, 851, or 500); and comparing the copy number of theSNP in the subject with a reference copy number, wherein the referencecopy number is associated with a known risk of developing SZ; andwherein the presence of a copy number of the SNP in the subject that isthe same as a reference copy number that is associated with SZ indicatesthat the risk that the subject will develop SZ.

Determining the identity or copy number of an allele can includeobtaining a sample comprising DNA from the subject, and determiningidentity or copy number of the nucleotide at the polymorphic site.Determining the identity of the nucleotide can include contacting thesample with a probe specific for a selected allele of the polymorphism,and detecting the formation of complexes between the probe and theselected allele of the polymorphism, wherein the formation of complexesbetween the probe and the test marker indicates the presence of theselected allele in the sample. Determining the identity of an allele caninclude determining the identity of the nucleotide at position 31 of oneof SEQ ID NOs: 1-1025. Determining the copy number of an allele caninclude contacting the sample with a probe specific for a selectedallele, detecting the formation of complexes between the probe and theselected allele of the polymorphism, and quantifying the complexes,wherein the quantification of the complexes indicates the copy number ofthe selected allele in the sample. A probe can include a fluorescentlabel, and quantifying the complexes comprises detecting intensity ofemission from the label. Determining the copy number of an allele caninclude detecting the absence or duplication of the allele in thesubject. A subject can be a patient having or suspected of having SZ. Asubject can have one or more risk factors associated with SZ. Riskfactors associated with SZ can include one or more of: a relativeafflicted with SZ; and a genetically based phenotypic trait associatedwith risk for a SZ. A subject can have exhibited or exhibits symptoms ofpsychosis. Methods can further include selecting or excluding a subjectfor enrollment in a clinical trial based on the identity of the allele.Methods can further include stratifying a subject population foranalysis of a clinical trial based on the identity of the allele in thesubjects. Methods can further include confirming a diagnosis of a SZusing psychometric instruments. Methods can further include selecting atreatment for SZ if an allele in the subject is the same as a referenceallele associated with SZ. Methods can further include selecting atreatment for SZ if the copy number of the allele in the subject is thesame as a reference copy number associated with SZ. Methods can furtherinclude administering the selected treatment to the subject. A treatmentcan include one or more of an anti-psychotic drug, an anti-depressantdrug, anti-anxiety drug, mood stabilizer, selective serotonin reuptakeinhibitor (SSRI), psychotherapy, or a stimulant. Methods can furtherinclude recording the identity of the allele in a tangible medium. Atangible medium can include a computer-readable disk, a solid statememory device, or an optical storage device.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention pertains. Although methods and materialssimilar or equivalent to those described herein can be used to practicethe invention, suitable methods and materials are described below. Allpublications, patent applications, patents, and other referencesmentioned herein are incorporated by reference in their entirety. Incase of conflict, the present specification, including definitions, willcontrol. In addition, the materials, methods, and examples areillustrative only and not intended to be limiting.

The details of one or more embodiments of the invention are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages of the invention will be apparent from thedescription and drawings, and from the claims.

DETAILED DESCRIPTION

This document provides methods for assessing genetic risk for developingSSDs based on evaluation of single nucleotide polymorphisms (SNPs) forgenes relating to SSDs including schizophrenia (SZ), schizotypalpersonality disorder (SPD), and schizoaffective disorder (SD). Asdescribed herein, bioinformatic and genetic analyses provided evidenceof association of the disclosed SNPs and haplotypes SZ. Specific allelicand copy number variants identified herein can be used to assess geneticrisk.

DEFINITIONS

As used herein, an “allele” is one of a pair or series of geneticvariants of a polymorphism at a specific genomic location. An “SZ riskallele” is an allele that is associated with increased risk ofdeveloping SZ. An “SZ allele” is an allele that is statisticallyassociated with a diagnosis of SZ.

As used herein, “genotype” refers to the diploid combination of allelesfor a given genetic polymorphism. A homozygous subject carries twocopies of the same allele and a heterozygous subject carries twodifferent alleles.

As used herein, “genetic model” refers to the manner in which an alleleinfluences risk or differential diagnosis. In a “dominant model” theallele impacts the clinical state to the same extent whether present inone copy or two copies, i.e., whether homozygous or heterozygous. In a“recessive model” the allele impacts the clinical state only whenhomozygous. In an “additive model” the allele impacts the clinical statein proportion to the number of copies present, i.e., the homozygousstate has twice the impact of the heterozygous state.

As used herein, a “haplotype” is one or a set of signature geneticchanges (polymorphisms) that are normally grouped closely together onthe DNA strand, and are usually inherited as a group; the polymorphismsare also referred to herein as “markers.” A “haplotype” as used hereinis information regarding the presence or absence of one or more geneticmarkers in a given chromosomal region in a subject. A haplotype canconsist of a variety of genetic markers, including indels (insertions ordeletions of the DNA at particular locations on the chromosome); singlenucleotide polymorphisms (SNPs) in which a particular nucleotide ischanged; microsatellites; and minisatellites.

Microsatellites (sometimes referred to as a variable number of tandemrepeats or VNTRs) are short segments of DNA that have a repeatedsequence, usually about 2 to 5 nucleotides long (e.g., CACACA), thattend to occur in non-coding DNA. Changes in the microsatellitessometimes occur during the genetic recombination of sexual reproduction,increasing or decreasing the number of repeats found at an allele,changing the length of the allele. Microsatellite markers are stable,polymorphic, easily analyzed and occur regularly throughout the genome,making them especially suitable for genetic analysis.

“Copy number variation” (CNV), as used herein, refers to variation fromthe normal diploid condition for a gene or polymorphism. Individualsegments of human chromosomes can be deleted or duplicated such that thesubject's two chromosome carry fewer than two copies of the gene orpolymorphism (a deletion or deficiency) or two or more copies (aduplication).

“Linkage disequilibrium” refers to when the observed frequencies ofhaplotypes in a population does not agree with haplotype frequenciespredicted by multiplying together the frequency of individual geneticmarkers in each haplotype.

The term “chromosome” as used herein refers to a gene carrier of a cellthat is derived from chromatin and comprises DNA and protein components(e.g., histones). The conventional internationally recognized individualhuman genome chromosome numbering identification system is employedherein. The size of an individual chromosome can vary from one type toanother with a given multi-chromosomal genome and from one genome toanother. In the case of the human genome, the entire DNA mass of a givenchromosome is usually greater than about 100,000,000 base pairs. Forexample, the size of the entire human genome is about 3×10⁹ base pairs.

The term “gene” refers to a DNA sequence in a chromosome that codes fora product (either RNA or its translation product, a polypeptide). A genecontains a coding region and includes regions preceding and followingthe coding region (termed respectively “leader” and “trailer”). Thecoding region is comprised of a plurality of coding segments (“exons”)and intervening sequences (“introns”) between individual codingsegments.

The term “probe” refers to an oligonucleotide. A probe can be singlestranded at the time of hybridization to a target. As used herein,probes include primers, i.e., oligonucleotides that can be used to primea reaction, e.g., a PCR reaction.

The term “label” or “label containing moiety” refers in a moiety capableof detection, such as a radioactive isotope or group containing same,and nonisotopic labels, such as enzymes, biotin, avidin, streptavidin,digoxygenin, luminescent agents, dyes, haptens, and the like.Luminescent agents, depending upon the source of exciting energy, can beclassified as radioluminescent, chemiluminescent, bioluminescent, andphotoluminescent (including fluorescent and phosphorescent). A probedescribed herein can be bound, e.g., chemically bound tolabel-containing moieties or can be suitable to be so bound. The probecan be directly or indirectly labeled.

The term “direct label probe” (or “directly labeled probe”) refers to anucleic acid probe whose label after hybrid formation with a target isdetectable without further reactive processing of hybrid. The term“indirect label probe” (or “indirectly labeled probe”) refers to anucleic acid probe whose label after hybrid formation with a target isfurther reacted in subsequent processing with one or more reagents toassociate therewith one or more moieties that finally result in adetectable entity.

The terms “target,” “DNA target,” or “DNA target region” refers to anucleotide sequence that occurs at a specific chromosomal location. Eachsuch sequence or portion is preferably at least partially, singlestranded (e.g., denatured) at the time of hybridization. When the targetnucleotide sequences are located only in a single region or fraction ofa given chromosome, the term “target region” is sometimes used. Targetsfor hybridization can be derived from specimens which include, but arenot limited to, chromosomes or regions of chromosomes in normal,diseased or malignant human cells, either interphase or at any state ofmeiosis or mitosis, and either extracted or derived from living orpostmortem tissues, organs or fluids; germinal cells including sperm andegg cells, or cells from zygotes, fetuses, or embryos, or chorionic oramniotic cells, or cells from any other germinating body; cells grown invitro, from either long-term or short-term culture, and either normal,immortalized or transformed; inter- or intraspecific hybrids ofdifferent types of cells or differentiation states of these cells;individual chromosomes or portions of chromosomes, or translocated,deleted or other damaged chromosomes, isolated by any of a number ofmeans known to those with skill in the art, including libraries of suchchromosomes cloned and propagated in prokaryotic or other cloningvectors, or amplified in vitro by means well known to those with skill;or any forensic material, including but not limited to blood, or othersamples.

The term “hybrid” refers to the product of a hybridization procedurebetween a probe and a target.

The term “hybridizing conditions” has general reference to thecombinations of conditions that are employable in a given hybridizationprocedure to produce hybrids, such conditions typically involvingcontrolled temperature, liquid phase, and contact between a probe (orprobe composition) and a target. Conveniently and preferably, at leastone denaturation step precedes a step wherein a probe or probecomposition is contacted with a target. Guidance for performinghybridization reactions can be found in Ausubel et al., CurrentProtocols in Molecular Biology, John Wiley & Sons, N.Y. (2003),6.3.1-6.3.6. Aqueous and nonaqueous methods are described in thatreference and either can be used. Hybridization conditions referred toherein are a 50% formamide, 2×SSC wash for 10 minutes at 45° C. followedby a 2×SSC wash for 10 minutes at 37° C.

Calculations of “identity” between two sequences can be performed asfollows. The sequences are aligned for optimal comparison purposes(e.g., gaps can be introduced in one or both of a first and a secondnucleic acid sequence for optimal alignment and non-identical sequencescan be disregarded for comparison purposes). The length of a sequencealigned for comparison purposes is at least 30% (e.g., at least 40%,50%, 60%, 70%, 80%, 90% or 100%) of the length of the referencesequence. The nucleotides at corresponding nucleotide positions are thencompared. When a position in the first sequence is occupied by the samenucleotide as the corresponding position in the second sequence, thenthe molecules are identical at that position. The percent identitybetween the two sequences is a function of the number of identicalpositions shared by the sequences, taking into account the number ofgaps, and the length of each gap, which need to be introduced foroptimal alignment of the two sequences.

The comparison of sequences and determination of percent identitybetween two sequences can be accomplished using a mathematicalalgorithm. In some embodiments, the percent identity between twonucleotide sequences is determined using the GAP program in the GCGsoftware package, using a Blossum 62 scoring matrix with a gap penaltyof 12, a gap extend penalty of 4, and a frameshift gap penalty of 5.

As used herein, the term “substantially identical” is used to refer to afirst nucleotide sequence that contains a sufficient number of identicalnucleotides to a second nucleotide sequence such that the first andsecond nucleotide sequences have similar activities. Nucleotidesequences that are substantially identical are at least 80% (e.g., 85%,90%, 95%, 97% or more) identical.

The term “nonspecific binding DNA” refers to DNA which is complementaryto DNA segments of a probe, which DNA occurs in at least one otherposition in a genome, outside of a selected chromosomal target regionwithin that genome. An example of nonspecific binding DNA comprises aclass of DNA repeated segments whose members commonly occur in more thanone chromosome or chromosome region. Such common repetitive segmentstend to hybridize to a greater extent than other DNA segments that arepresent in probe composition.

As used herein, the term “stratification” refers to the creation of adistinction between subjects on the basis of a characteristic orcharacteristics of the subjects. Generally, in the context of clinicaltrials, the distinction is used to distinguish responses or effects indifferent sets of patients distinguished according to the stratificationparameters. In some embodiments, stratification includes distinction ofsubject groups based on the presence or absence of particular markers orhaplotypes described herein. The stratification can be performed, e.g.,in the course of analysis, or can be used in creation of distinct groupsor in other ways.

Methods of Diagnoses and Evaluation of Risk

Described herein are a variety of methods for determining susceptibilityto an SSD (e.g., SZ). “Susceptibility” does not necessarily mean thatthe subject will develop an SSD (e.g., SZ), but rather that the subjectis, in a statistical sense, more likely to develop SZ than an averagemember of the population, i.e., has an increased risk of developing anSSD (e.g., SZ). As used herein, susceptibility to an SSD exists if thesubject has a genetic variation, e.g., an allele or CNV, associated withan increased risk of an SSD (e.g., SZ) as described herein. Ascertainingwhether the subject has such an allele or CNV is included in the conceptof diagnosing susceptibility to an SSD (e.g., SZ) as used herein. Suchdetermination is useful, for example, for purposes of diagnosis,treatment selection, and genetic counseling. Thus, the methods describedherein can include obtaining a haplotype associated with an increasedrisk of an SSD (e.g., SZ) as described herein for the subject.

As used herein, “determining the identity of an allele” or “determiningcopy number” includes obtaining information regarding the identity,number, presence or absence of one or more specific alleles or SNPs in asubject. Determining the identity of an allele or determining copynumber can, but need not, include obtaining a sample comprising DNA froma subject, and/or assessing the identity, copy number, presence orabsence of one or more genetic markers in the sample. The individual ororganization who performs the determination need not actually carry outthe physical analysis of a sample from a subject; the methods caninclude using information obtained by analysis of the sample by a thirdparty. Thus the methods can include steps that occur at more than onesite. For example, a sample can be obtained from a subject at a firstsite, such as at a health care provider, or at the subject's home in thecase of a self-testing kit. The sample can be analyzed at the same or asecond site, e.g., at a laboratory or other testing facility.

Determining the identity of an allele or copy number of a SNP can alsoinclude or consist of reviewing a subject's medical history, where themedical history includes information regarding the identity, copynumber, presence or absence of one or more alleles or SNPs in thesubject, e.g., results of a genetic test.

In some embodiments, to determine the identity of an allele or copynumber/presence/absence of an allele or genotype described herein, abiological sample that includes nucleated cells (such as blood, a cheekswab or mouthwash) is prepared and analyzed for the copy number,presence or absence of preselected markers. Such diagnoses may beperformed by diagnostic laboratories, or, alternatively, diagnostic kitscan be manufactured and sold to health care providers or to privateindividuals for self-diagnosis. Diagnostic or prognostic tests can beperformed as described herein or using well known techniques, such asdescribed in U.S. Pat. No. 5,800,998.

Results of these tests, and optionally interpretive information, can bereturned to the subject, the health care provider or to a third partypayor. The results can be used in a number of ways. The information canbe, e.g., communicated to the tested subject, e.g., with a prognosis andoptionally interpretive materials that help the subject understand thetest results and prognosis. The information can be used, e.g., by ahealth care provider, to determine whether to administer a specificdrug, or whether a subject should be assigned to a specific category,e.g., a category associated with a specific disease endophenotype, orwith drug response or non-response. The information can be used, e.g.,by a third party payer such as a healthcare payer (e.g., insurancecompany or HMO) or other agency, to determine whether or not toreimburse a health care provider for services to the subject, or whetherto approve the provision of services to the subject. For example, thehealthcare payer may decide to reimburse a health care provider fortreatments for SZ if the subject has SZ or has an increased risk ofdeveloping SZ. The presence or absence of the allele or genotype in apatient may be ascertained by using any of the methods described herein.

Alleles and Genotypes Associated with SSDs

This document provides methods for diagnosing and assessing genetic riskbased on evaluation of single nucleotide polymorphisms (SNPs) for genesrelating to SZ-spectrum disorders including schizophrenia (SZ),schizotypal personality disorder (SPD) and schizoaffective disorder(SD). Tables 1-3 and Table A list specific exemplary SNPs that can beused to capture significant haplotype variation in these genes. One ofskill in the art will appreciate that additional variants can beidentified via TDT using families with multiple affected individuals(such as those collected CCGS) and verified by Case/Control comparisons,e.g., using the methods and markers presented herein. Using the SNPmarkers described herein, one can determine the alleles, copy number,genotypes or haplotypes in these genes relating to diagnosis or geneticrisk of developing SZ. This information can then be used to determinerisk of developing SZ, or for making a diagnosis of SZ. The allelic andgenotypic variants thus identified can be used for diagnosis and forassessing genetic risk.

In some embodiments, the methods can include determining the presence ofa haplotype that includes one or more polymorphisms near D22S526 and/orthe polymorphisms in the Sult4a1 gene and/or polymorphisms within 1linkage disequilibrium unit (LDU) of these markers, e.g., as describedin U.S. Pat. Pub. No. US2006/0177851, incorporated herein in itsentirety.

Linkage Disequilibrium Analysis

Linkage disequilibrium (LD) is a measure of the degree of associationbetween alleles in a population. One of skill in the art will appreciatethat haplotypes involving markers in LD with the polymorphisms describedherein can also be used in a similar manner to those described herein.Methods of calculating LD are known in the art (see, e.g., Morton etal., Proc. Natl. Acad. Sci. USA 98(9):5217-21 (2001); Tapper et al.,Proc. Natl. Acad. Sci. USA 102(33):11835-11839 (2005); Maniatis et al.,Proc. Natl. Acad. Sci. USA 99:2228-2233 (2002)). Thus, in some cases,the methods can include analysis of polymorphisms that are in LD with apolymorphism described herein. Methods are known in the art foridentifying such polymorphisms; for example, the International HapMapProject provides a public database that can be used, see hapmap.org, aswell as The International HapMap Consortium, Nature 426:789-796 (2003),and The International HapMap Consortium, Nature 437:1299-1320 (2005).Generally, it will be desirable to use a HapMap constructed using datafrom individuals who share ethnicity with the subject. For example, aHapMap for African Americans would ideally be used to identify markersin LD with an exemplary marker described herein for use in genotyping asubject of African American descent.

Alternatively, methods described herein can include analysis ofpolymorphisms that show a correlation coefficient (r²) of value ≧0.5with the markers described herein. Results can be obtained from on linepublic resources such as HapMap.org on the World Wide Web. Thecorrelation coefficient is a measure of LD, and reflects the degree towhich alleles at two loci (for example, two SNPs) occur together, suchthat an allele at one SNP position can predict the correlated allele ata second SNP position, in the case where r² is >0.5.

Identifying Additional Genetic Markers

In general, genetic markers can be identified using any of a number ofmethods well known in the art. For example, numerous polymorphisms inthe regions described herein are known to exist and are available inpublic databases, which can be searched using methods and algorithmsknown in the art. Alternately, polymorphisms can be identified bysequencing either genomic DNA or cDNA in the region in which it isdesired to find a polymorphism. According to one approach, primers aredesigned to amplify such a region, and DNA from a subject is obtainedand amplified. The DNA is sequenced, and the sequence (referred to as a“subject sequence” or “test sequence”) is compared with a referencesequence, which can represent the “normal” or “wild type” sequence, orthe “affected” sequence. In some embodiments, a reference sequence canbe from, for example, the human draft genome sequence, publiclyavailable in various databases, or a sequence deposited in a databasesuch as GenBank. In some embodiments, the reference sequence is acomposite of ethnically diverse individuals.

In general, if sequencing reveals a difference between the sequencedregion and the reference sequence, a polymorphism has been identified.The fact that a difference in nucleotide sequence is identified at aparticular site that determines that a polymorphism exists at that site.In most instances, particularly in the case of SNPs, only twopolymorphic variants will exist at any location. However, in the case ofSNPs, up to four variants may exist since there are four naturallyoccurring nucleotides in DNA. Other polymorphisms, such as insertionsand deletions, may have more than four alleles.

The methods described herein can also include determining the presenceor absence of other markers known or suspected to be associated withrisk of bipolar disorder (BD) and/or SZ, or differentially inherited inBD versus SZ. In some embodiments, the methods include determining thepresence or absence of one or more other markers that are or may beassociated with BD or SZ, e.g., in one or more genes, e.g., e.g., asdescribed in WO 2009/092032, WO 2009/089120, WO 2009/082743,US2006/0177851, and US2009/0012371 incorporated herein in theirentirety. See also, e.g., OMIM entry no. 181500 (SCZD).

Methods of Determining the Identity of an Allele or Obtaining a Genotype

The methods described herein include determining the identity, copynumber, presence, or absence of alleles or genotypes associated withdiagnosis or risk of developing SZ. In some embodiments, an associationwith SZ is determined by the statistical likelihood of the presence ofan allele or genotype in an individual with SZ, e.g., an unrelatedindividual or a first or second-degree relation of the subject, andoptionally the statistical likelihood of the absence of the same allele,copy number, or genotype in an unaffected reference individual, e.g., anunrelated individual or a first or second-degree relation of thesubject. Thus the methods can include obtaining and analyzing a samplefrom one or more suitable reference individuals.

Samples that are suitable for use in the methods described hereincontain genetic material, e.g., genomic DNA (gDNA). Genomic DNA istypically extracted from biological samples such as blood or mucosalscrapings of the lining of the mouth, but can be extracted from otherbiological samples including urine or expectorant. The sample itselfwill typically consist of nucleated cells (e.g., blood or buccal cells)or tissue removed from the subject. The subject can be an adult, child,fetus, or embryo. In some embodiments, the sample is obtainedprenatally, either from a fetus or embryo or from the mother (e.g., fromfetal or embryonic cells in the maternal circulation). Methods andreagents are known in the art for obtaining, processing, and analyzingsamples. In some embodiments, the sample is obtained with the assistanceof a health care provider, e.g., to draw blood. In some embodiments, thesample is obtained without the assistance of a health care provider,e.g., where the sample is obtained non-invasively, such as a samplecomprising buccal cells that is obtained using a buccal swab or brush,or a mouthwash sample.

In some cases, a biological sample may be processed for DNA isolation.For example, DNA in a cell or tissue sample can be separated from othercomponents of the sample. Cells can be harvested from a biologicalsample using standard techniques known in the art. For example, cellscan be harvested by centrifuging a cell sample and resuspending thepelleted cells. The cells can be resuspended in a buffered solution suchas phosphate-buffered saline (PBS). After centrifuging the cellsuspension to obtain a cell pellet, the cells can be lysed to extractDNA, e.g., gDNA. See, e.g., Ausubel et al., 2003, supra. The sample canbe concentrated and/or purified to isolate DNA. All samples obtainedfrom a subject, including those subjected to any sort of furtherprocessing, are considered to be obtained from the subject. Routinemethods can be used to extract genomic DNA from a biological sample,including, for example, phenol extraction. Alternatively, genomic DNAcan be extracted with kits such as the QIAamp® Tissue Kit (Qiagen,Chatsworth, Calif.) and the Wizard® Genomic DNA purification kit(Promega). Non-limiting examples of sources of samples include urine,blood, and tissue.

The copy number, absence or presence of an allele or genotype associatedSZ as described herein can be determined using methods known in the art.For example, gel electrophoresis, capillary electrophoresis, sizeexclusion chromatography, sequencing, and/or arrays can be used todetect the presence or absence of the allele or genotype. Amplificationof nucleic acids, where desirable, can be accomplished using methodsknown in the art, e.g., PCR. In one example, a sample (e.g., a samplecomprising genomic DNA), is obtained from a subject. The DNA in thesample is then examined to identify or detect the presence of an alleleor genotype as described herein. The allele or genotype can beidentified or determined by any method described herein, e.g., bysequencing or by hybridization of the gene in the genomic DNA, RNA, orcDNA to a nucleic acid probe, e.g., a DNA probe (which includes cDNA andoligonucleotide probes) or an RNA probe. The nucleic acid probe can bedesigned to specifically or preferentially hybridize with a particularpolymorphic variant.

Other methods of nucleic acid analysis can include direct manualsequencing (Church and Gilbert, Proc. Natl. Acad. Sci. USA 81:1991-1995(1988); Sanger et al., Proc. Natl. Acad. Sci. USA 74:5463-5467 (1977);Beavis et al., U.S. Pat. No. 5,288,644); automated fluorescentsequencing; single-stranded conformation polymorphism assays (SSCP)(Schafer et al., Nat. Biotechnol. 15:33-39 (1995)); clamped denaturinggel electrophoresis (CDGE); two-dimensional gel electrophoresis (2DGE orTDGE); conformational sensitive gel electrophoresis (CSGE); denaturinggradient gel electrophoresis (DGGE) (Sheffield et al., Proc. Natl. Acad.Sci. USA 86:232-236 (1989)); denaturing high performance liquidchromatography (DHPLC, Underhill et al., Genome Res. 7:996-1005 (1997));infrared matrix-assisted laser desorption/ionization (IR-MALDI) massspectrometry (WO 99/57318); mobility shift analysis (Orita et al., Proc.Natl. Acad. Sci. USA 86:2766-2770 (1989)); restriction enzyme analysis(Flavell et al., Cell 15:25 (1978); Geever et al., Proc. Natl. Acad.Sci. USA 78:5081 (1981)); quantitative real-time PCR (Raca et al., GenetTest 8(4):387-94 (2004)); heteroduplex analysis; chemical mismatchcleavage (CMC) (Cotton et al., Proc. Natl. Acad. Sci. USA 85:4397-4401(1985)); RNase protection assays (Myers et al., Science 230:1242(1985)); use of polypeptides that recognize nucleotide mismatches, e.g.,E. coli mutS protein; allele-specific PCR, and combinations of suchmethods. See, e.g., Gerber et al., U.S. Patent Publication No.2004/0014095 which is incorporated herein by reference in its entirety.

Sequence analysis can also be used to detect specific polymorphicvariants. For example, polymorphic variants can be detected bysequencing exons, introns, 5′ untranslated sequences, or 3′ untranslatedsequences. A sample comprising DNA or RNA is obtained from the subject.PCR or other appropriate methods can be used to amplify a portionencompassing the polymorphic site, if desired. The sequence is thenascertained, using any standard method, and the presence of apolymorphic variant is determined. Real-time pyrophosphate DNAsequencing is yet another approach to detection of polymorphisms andpolymorphic variants (Alderborn et al., Genome Research 10(8):1249-1258(2000)). Additional methods include, for example, PCR amplification incombination with denaturing high performance liquid chromatography(dHPLC) (Underhill et al., Genome Research 7(10):996-1005 (1997)).

In order to detect polymorphisms and/or polymorphic variants, it willfrequently be desirable to amplify a portion of genomic DNA (gDNA)encompassing the polymorphic site. Such regions can be amplified andisolated by PCR using oligonucleotide primers designed based on genomicand/or cDNA sequences that flank the site. PCR refers to procedures inwhich target nucleic acid (e.g., genomic DNA) is amplified in a mannersimilar to that described in U.S. Pat. No. 4,683,195, and subsequentmodifications of the procedure described therein. Generally, sequenceinformation from the ends of the region of interest or beyond are usedto design oligonucleotide primers that are identical or similar insequence to opposite strands of a potential template to be amplified.See e.g., PCR Primer: A Laboratory Manual, Dieffenbach and Dveksler,(Eds.); McPherson et al., PCR Basics: From Background to Bench (SpringerVerlag, 2000); Mattila et al., Nucleic Acids Res., 19:4967 (1991);Eckert et al., PCR Methods and Applications, 1:17 (1991); PCR (eds.McPherson et al., IRL Press, Oxford); and U.S. Pat. No. 4,683,202. Otheramplification methods that may be employed include the ligase chainreaction (LCR) (Wu and Wallace, Genomics 4:560 (1989), Landegren et al.,Science 241:1077 (1988), transcription amplification (Kwoh et al., Proc.Natl. Acad. Sci. USA 86:1173 (1989)), self-sustained sequencereplication (Guatelli et al., Proc. Nat. Acad. Sci. USA 87:1874 (1990)),and nucleic acid based sequence amplification (NASBA). Guidelines forselecting primers for PCR amplification are well known in the art. See,e.g., McPherson et al., PCR Basics: From Background to Bench,Springer-Verlag, 2000. A variety of computer programs for designingprimers are available, e.g., ‘Oligo’ (National Biosciences, Inc,Plymouth Minn.), MacVector (Kodak/IBI), and the GCG suite of sequenceanalysis programs (Genetics Computer Group, Madison, Wis. 53711).

In some cases, PCR conditions and primers can be developed that amplifya product only when the variant allele is present or only when the wildtype allele is present (MSPCR or allele-specific PCR). For example,patient DNA and a control can be amplified separately using either awild type primer or a primer specific for the variant allele. Each setof reactions is then examined for the presence of amplification productsusing standard methods to visualize the DNA. For example, the reactionscan be electrophoresed through an agarose gel and the DNA visualized bystaining with ethidium bromide or other DNA intercalating dye. In DNAsamples from heterozygous patients, reaction products would be detectedin each reaction.

Real-time quantitative PCR can also be used to determine copy number.Quantitative PCR permits both detection and quantification of specificDNA sequence in a sample as an absolute number of copies or as arelative amount when normalized to DNA input or other normalizing genes.A key feature of quantitative PCR is that the amplified DNA product isquantified in real-time as it accumulates in the reaction after eachamplification cycle. Methods of quantification can include the use offluorescent dyes that intercalate with double-stranded DNA, and modifiedDNA oligonucleotide probes that fluoresce when hybridized with acomplementary DNA.

The first report of extensive copy number variation (CNV) in the humangenome used intensity analysis of microarray data to document numerousexamples of genes that vary in copy number (Redon et al., Nature444(7118):444-54 (2006)). Subsequent studies have shown that certaincopy number variants are associated with complex genetic diseases suchas SZ (Walsh et al., Science 320(5875):539-43 (2008); and Stone et al.,Nature 455(7210):237-41 (2008)).

In some embodiments, a peptide nucleic acid (PNA) probe can be usedinstead of a nucleic acid probe in the hybridization methods describedabove. PNA is a DNA mimetic with a peptide-like, inorganic backbone,e.g., N-(2-aminoethyl)glycine units, with an organic base (A, G, C, T orU) attached to the glycine nitrogen via a methylene carbonyl linker(see, e.g., Nielsen et al., Bioconjugate Chemistry, The AmericanChemical Society, 5:1 (1994)). The PNA probe can be designed tospecifically hybridize to a nucleic acid comprising a polymorphicvariant conferring susceptibility to or indicative of the presence of,for example, SZ.

In some cases, allele-specific oligonucleotides can also be used todetect the presence of a polymorphic variant. For example, polymorphicvariants can be detected by performing allele-specific hybridization orallele-specific restriction digests. Allele specific hybridization is anexample of a method that can be used to detect sequence variants,including complete haplotypes of a subject (e.g., a mammal such as ahuman). See Stoneking et al., Am. J. Hum. Genet. 48:370-382 (1991); andPrince et al., Genome Res. 11:152-162 (2001). An “allele-specificoligonucleotide” (also referred to herein as an “allele-specificoligonucleotide probe”) is an oligonucleotide that is specific forparticular a polymorphism can be prepared using standard methods (seeAusubel et al., Current Protocols in Molecular Biology, supra).Allele-specific oligonucleotide probes typically can be approximately10-50 base pairs, preferably approximately 15-30 base pairs, thatspecifically hybridizes to a nucleic acid region that contains apolymorphism. Hybridization conditions are selected such that a nucleicacid probe can specifically bind to the sequence of interest, e.g., thevariant nucleic acid sequence. Such hybridizations typically areperformed under high stringency as some sequence variants include only asingle nucleotide difference. In some cases, dot-blot hybridization ofamplified oligonucleotides with allele-specific oligonucleotide (ASO)probes can be performed. See, for example, Saiki et al., Nature (London)324:163-166 (1986).

In some embodiments, allele-specific restriction digest analysis can beused to detect the existence of a polymorphic variant of a polymorphism,if alternate polymorphic variants of the polymorphism result in thecreation or elimination of a restriction site. Allele-specificrestriction digests can be performed in the following manner. A samplecontaining genomic DNA is obtained from the individual and genomic DNAis isolated for analysis. For nucleotide sequence variants thatintroduce a restriction site, restriction digest with the particularrestriction enzyme can differentiate the alleles. In some cases,polymerase chain reaction (PCR) can be used to amplify a regioncomprising the polymorphic site, and restriction fragment lengthpolymorphism analysis is conducted (see Ausubel et al., CurrentProtocols in Molecular Biology, supra). The digestion pattern of therelevant DNA fragment indicates the presence or absence of a particularpolymorphic variant of the polymorphism and is therefore indicative ofthe presence or absence of susceptibility to SZ. For sequence variantsthat do not alter a common restriction site, mutagenic primers can bedesigned that introduce a restriction site when the variant allele ispresent or when the wild type allele is present. For example, a portionof a nucleic acid can be amplified using the mutagenic primer and a wildtype primer, followed by digest with the appropriate restrictionendonuclease.

In some embodiments, fluorescence polarization template-directeddye-terminator incorporation (FP-TDI) is used to determine which ofmultiple polymorphic variants of a polymorphism is present in a subject(Chen et al., Genome Research 9(5):492-498 (1999)). Rather thaninvolving use of allele-specific probes or primers, this method employsprimers that terminate adjacent to a polymorphic site, so that extensionof the primer by a single nucleotide results in incorporation of anucleotide complementary to the polymorphic variant at the polymorphicsite.

In some cases, DNA containing an amplified portion may be dot-blotted,using standard methods (see Ausubel et al., Current Protocols inMolecular Biology, supra), and the blot contacted with theoligonucleotide probe. The presence of specific hybridization of theprobe to the DNA is then detected. Specific hybridization of anallele-specific oligonucleotide probe (specific for a polymorphicvariant indicative of susceptibility to an SSD (e.g., SZ)) to DNA fromthe subject is indicative of susceptibility to an SSD (e.g., SZ).

The methods can include determining the genotype of a subject withrespect to both copies of the polymorphic site present in the genome.For example, the complete genotype may be characterized as −/−, as −/+,or as +/+, where a minus sign indicates the presence of the reference orwild type sequence at the polymorphic site, and the plus sign indicatesthe presence of a polymorphic variant other than the reference sequence.If multiple polymorphic variants exist at a site, this can beappropriately indicated by specifying which ones are present in thesubject. Any of the detection means described herein can be used todetermine the genotype of a subject with respect to one or both copiesof the polymorphism present in the subject's genome.

Methods of nucleic acid analysis to detect polymorphisms and/orpolymorphic variants can include, e.g., microarray analysis.Hybridization methods, such as Southern analysis, Northern analysis, orin situ hybridizations, can also be used (see Ausubel et al., CurrentProtocols in Molecular Biology, eds., John Wiley & Sons (2003)). Todetect microdeletions, fluorescence in situ hybridization (FISH) usingDNA probes that are directed to a putatively deleted region in achromosome can be used. For example, probes that detect all or a part ofa microsatellite marker can be used to detect microdeletions in theregion that contains that marker.

In some embodiments, it is desirable to employ methods that can detectthe presence of multiple polymorphisms (e.g., polymorphic variants at aplurality of polymorphic sites) in parallel or substantiallysimultaneously. Oligonucleotide arrays represent one suitable means fordoing so. Other methods, including methods in which reactions (e.g.,amplification, hybridization) are performed in individual vessels, e.g.,within individual wells of a multi-well plate or other vessel may alsobe performed so as to detect the presence of multiple polymorphicvariants (e.g., polymorphic variants at a plurality of polymorphicsites) in parallel or substantially simultaneously according to certainembodiments.

Nucleic acid probes can be used to detect and/or quantify the presenceof a particular target nucleic acid sequence within a sample of nucleicacid sequences, e.g., as hybridization probes, or to amplify aparticular target sequence within a sample, e.g., as a primer. Probeshave a complimentary nucleic acid sequence that selectively hybridizesto the target nucleic acid sequence. In order for a probe to hybridizeto a target sequence, the hybridization probe must have sufficientidentity with the target sequence, i.e., at least 70% (e.g., 80%, 90%,95%, 98% or more) identity to the target sequence. The probe sequencemust also be sufficiently long so that the probe exhibits selectivityfor the target sequence over non-target sequences. For example, theprobe will be at least 20 (e.g., 25, 30, 35, 50, 100, 200, 300, 400,500, 600, 700, 800, 900 or more) nucleotides in length. In someembodiments, the probes are not more than 30, 50, 100, 200, 300, 500,750, or 1000 nucleotides in length. Probes are typically about 20 toabout 1×10⁶ nucleotides in length. Probes include primers, whichgenerally refers to a single-stranded oligonucleotide probe that can actas a point of initiation of template-directed DNA synthesis usingmethods such as PCR (polymerase chain reaction), LCR (ligase chainreaction), etc., for amplification of a target sequence.

The probe can be a test probe such as a probe that can be used to detectpolymorphisms in a region described herein (e.g., polymorphisms asdescribed herein). For example, the probe can hybridize to an alleledescribed herein. In some embodiments, the probe can bind to anothermarker sequence associated with SZ, SPD, SD or BD as described herein.

Control probes can also be used. For example, a probe that binds a lessvariable sequence, e.g., repetitive DNA associated with a centromere ofa chromosome, can be used as a control. Probes that hybridize withvarious centromeric DNA and locus-specific DNA are availablecommercially, for example, from Vysis, Inc. (Downers Grove, Ill.),Molecular Probes, Inc. (Eugene, Oreg.), or from Cytocell (Oxfordshire,UK). Probe sets are available commercially such from Applied Biosystems,e.g., the Assays-on-Demand SNP kits Alternatively, probes can besynthesized, e.g., chemically or in vitro, or made from chromosomal orgenomic DNA through standard techniques. For example, sources of DNAthat can be used include genomic DNA, cloned DNA sequences, somatic cellhybrids that contain one, or a part of one, human chromosome along withthe normal chromosome complement of the host, and chromosomes purifiedby flow cytometry or microdissection. The region of interest can beisolated through cloning, or by site-specific amplification via thepolymerase chain reaction (PCR). See, for example, Nath and Johnson,Biotechnic. Histochem. 73(1):6-22 (1998); Wheeless et al., Cytometry17:319-326 (1994); and U.S. Pat. No. 5,491,224.

In some embodiments, the probes are labeled, e.g., by direct labeling,with a fluorophore, an organic molecule that fluoresces after absorbinglight of lower wavelength/higher energy. A directly labeled fluorophoreallows the probe to be visualized without a secondary detectionmolecule. After covalently attaching a fluorophore to a nucleotide, thenucleotide can be directly incorporated into the probe with standardtechniques such as nick translation, random priming, and PCR labeling.Alternatively, deoxycytidine nucleotides within the probe can betransaminated with a linker. The fluorophore then is covalently attachedto the transaminated deoxycytidine nucleotides. See, e.g., U.S. Pat. No.5,491,224.

Fluorophores of different colors can be chosen such that each probe in aset can be distinctly visualized. For example, a combination of thefollowing fluorophores can be used: 7-amino-4-methylcoumarin-3-aceticacid (AMCA), TEXAS RED™ (Molecular Probes, Inc., Eugene, Oreg.),5-(and-6)-carboxy-X-rhodamine, lissamine rhodamine B,5-(and-6)-carboxyfluorescein, fluorescein-5-isothiocyanate (FITC),7-diethylaminocoumarin-3-carboxylic acid,tetramethylrhodamine-5-(and-6)-isothiocyanate,5-(and-6)-carboxytetramethylrhodamine, 7-hydroxycoumarin-3-carboxylicacid, 6-[fluorescein 5-(and-6)-carboxamido]hexanoic acid,N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a diaza-3-indacenepropionicacid, eosin-5-isothiocyanate, erythrosin-5-isothiocyanate, and CASCADE™blue acetylazide (Molecular Probes, Inc., Eugene, Oreg.). Fluorescentlylabeled probes can be viewed with a fluorescence microscope and anappropriate filter for each fluorophore, or by using dual or tripleband-pass filter sets to observe multiple fluorophores. See, forexample, U.S. Pat. No. 5,776,688. Alternatively, techniques such as flowcytometry can be used to examine the hybridization pattern of theprobes. Fluorescence-based arrays are also known in the art.

In other embodiments, the probes can be indirectly labeled with, e.g.,biotin or digoxygenin, or labeled with radioactive isotopes such as ³²Pand ³H. For example, a probe indirectly labeled with biotin can bedetected by avidin conjugated to a detectable marker. For example,avidin can be conjugated to an enzymatic marker such as alkalinephosphatase or horseradish peroxidase. Enzymatic markers can be detectedin standard colorimetric reactions using a substrate and/or a catalystfor the enzyme. Catalysts for alkaline phosphatase include5-bromo-4-chloro-3-indolylphosphate and nitro blue tetrazolium.Diaminobenzoate can be used as a catalyst for horseradish peroxidase.

In another aspect, this document features arrays that include asubstrate having a plurality of addressable areas, and methods of usingthem. At least one area of the plurality includes a nucleic acid probethat binds specifically to a sequence comprising a polymorphism listedin Tables 1-3 or Table A, and can be used to detect the absence orpresence of said polymorphism, e.g., one or more SNPs, microsatellites,minisatellites, or indels, as described herein, to determine or identifyan allele or genotype. For example, the array can include one or morenucleic acid probes that can be used to detect a polymorphism listed inTables 1-3 or Table A. In some embodiments, the array further includesat least one area that includes a nucleic acid probe that can be used tospecifically detect another marker associated with SZ or one associatedwith BD as described herein or known in the art. In some embodiments,the probes are nucleic acid capture probes.

Generally, microarray hybridization is performed by hybridizing anucleic acid of interest (e.g., a nucleic acid encompassing apolymorphic site) with the array and detecting hybridization usingnucleic acid probes. In some cases, the nucleic acid of interest isamplified prior to hybridization. Hybridization and detecting aregenerally carried out according to standard methods. See, e.g.,Published PCT Application Nos. WO 92/10092 and WO 95/11995, and U.S.Pat. No. 5,424,186. For example, the array can be scanned to determinethe position on the array to which the nucleic acid hybridizes. Thehybridization data obtained from the scan is typically in the form offluorescence intensities as a function of location on the array.

Arrays can be formed on substrates fabricated with materials such aspaper, glass, plastic (e.g., polypropylene, nylon, or polystyrene),polyacrylamide, nitrocellulose, silicon, optical fiber, or any othersuitable solid or semisolid support, and can be configured in a planar(e.g., glass plates, silicon chips) or three dimensional (e.g., pins,fibers, beads, particles, microtiter wells, capillaries) configuration.Methods for generating arrays are known in the art and include, e.g.,photolithographic methods (see, e.g., U.S. Pat. Nos. 5,143,854;5,510,270; and 5,527,681), mechanical methods (e.g., directed-flowmethods as described in U.S. Pat. No. 5,384,261), pin-based methods(e.g., as described in U.S. Pat. No. 5,288,514), and bead-basedtechniques (e.g., as described in PCT US/93/04145). The array typicallyincludes oligonucleotide hybridization probes capable of specificallyhybridizing to different polymorphic variants. Oligonucleotide probesthat exhibit differential or selective binding to polymorphic sites mayreadily be designed by one of ordinary skill in the art. For example, anoligonucleotide that is perfectly complementary to a sequence thatencompasses a polymorphic site (i.e., a sequence that includes thepolymorphic site, within it or at one end) will generally hybridizepreferentially to a nucleic acid comprising that sequence, as opposed toa nucleic acid comprising an alternate polymorphic variant.

Oligonucleotide probes forming an array may be attached to a substrateby any number of techniques, including, without limitation, (i) in situsynthesis (e.g., high-density oligonucleotide arrays) usingphotolithographic techniques; (ii) spotting/printing at medium to lowdensity on glass, nylon or nitrocellulose; (iii) by masking, and (iv) bydot-blotting on a nylon or nitrocellulose hybridization membrane.Oligonucleotides can be immobilized via a linker, including by covalent,ionic, or physical linkage. Linkers for immobilizing nucleic acids andpolypeptides, including reversible or cleavable linkers, are known inthe art. See, for example, U.S. Pat. No. 5,451,683 and WO98/20019.Alternatively, oligonucleotides can be non-covalently immobilized on asubstrate by hybridization to anchors, by means of magnetic beads, or ina fluid phase such as in microtiter wells or capillaries. Immobilizedoligonucleotide probes are typically about 20 nucleotides in length, butcan vary from about 10 nucleotides to about 1000 nucleotides in length.

Arrays can include multiple detection blocks (i.e., multiple groups ofprobes designed for detection of particular polymorphisms). Such arrayscan be used to analyze multiple different polymorphisms. Detectionblocks may be grouped within a single array or in multiple, separatearrays so that varying conditions (e.g., conditions optimized forparticular polymorphisms) may be used during the hybridization. Forexample, it may be desirable to provide for the detection of thosepolymorphisms that fall within G-C rich stretches of a genomic sequence,separately from those falling in A-T rich segments. General descriptionsof using oligonucleotide arrays for detection of polymorphisms can befound, for example, in U.S. Pat. Nos. 5,858,659 and 5,837,832. Inaddition to oligonucleotide arrays, cDNA arrays may be used similarly incertain embodiments.

The methods described herein can include providing an array as describedherein; contacting the array with a sample (e.g., a portion of genomicDNA that includes at least a portion of a human chromosome) and/oroptionally, a different portion of genomic DNA (e.g., a portion thatincludes a different portion of a human chromosome, e.g., includinganother region associated with SZ), and detecting binding of a nucleicacid from the sample to the array. Optionally, the method includesamplifying nucleic acid from the sample, e.g., genomic DNA that includesa portion of a human chromosome described herein, and, optionally, aregion that includes another region associated with SZ, prior to orduring contact with the array.

In some aspects, the methods described herein can include using an arraythat can ascertain differential expression patterns or copy numbers ofone or more genes in samples from normal and affected individuals (see,e.g., Redon et al., Nature 444(7118):444-54 (2006)). For example, arraysof probes to a marker described herein can be used to measurepolymorphisms between DNA from a subject having an SSD (e.g., SZ), andcontrol DNA, e.g., DNA obtained from an individual that does not haveSZ, SPD, or SD, and has no risk factors for an SSD (e.g., SZ). Since theclones on the array contain sequence tags, their positions on the arrayare accurately known relative to the genomic sequence. Differenthybridization patterns between DNA from an individual afflicted with anSSD (e.g., SZ) and DNA from a normal individual at areas in the arraycorresponding to markers in human chromosome 4p and/or 22q as describedherein, and, optionally, one or more other regions associated with anSSD (e.g., SZ), are indicative of a risk of SZ. Methods for arrayproduction, hybridization, and analysis are described, e.g., in Snijderset al., Nat. Genetics 29:263-264 (2001); Klein et al., Proc. Natl. Acad.Sci. USA 96:4494-4499 (1999); Albertson et al., Breast Cancer Researchand Treatment 78:289-298 (2003); and Snijders et al., “BAC microarraybased comparative genomic hybridization,” in: Zhao et al. (eds),Bacterial Artificial Chromosomes: Methods and Protocols, Methods inMolecular Biology, Humana Press, 2002.

In another aspect, this document provides methods of determining theabsence or presence of a haplotype associated with SZ as describedherein, using an array described above. The methods can includeproviding a two dimensional array having a plurality of addresses, eachaddress of the plurality being positionally distinguishable from eachother address of the plurality having a unique nucleic acid captureprobe, contacting the array with a first sample from a test subject whois suspected of having or being at risk for SZ, and comparing thebinding of the first sample with one or more references, e.g., bindingof a sample from a subject who is known to have an SSD (e.g., SZ),and/or binding of a sample from a subject who is unaffected, e.g., acontrol sample from a subject who neither has, nor has any risk factorsfor an SSD (e.g., SZ). In some embodiments, the methods can includecontacting the array with a second sample from a subject who has an SSD(e.g., SZ); and comparing the binding of the first sample with thebinding of the second sample. In some embodiments, the methods caninclude contacting the array with a third sample from a cell or subjectthat does not have SZ and is not at risk for SZ; and comparing thebinding of the first sample with the binding of the third sample. Insome embodiments, the second and third samples are from first orsecond-degree relatives of the test subject. In the case of a nucleicacid hybridization, binding with a capture probe at an address of theplurality, can be detected by any method known in the art, e.g., bydetection of a signal generated from a label attached to the nucleicacid.

Communicating a Diagnosis or Risk Assessment

This document also provides methods and materials to assist medical orresearch professionals in determining whether or not a subject has or isat risk for developing an SSD (e.g., SZ). Medical professionals can be,for example, doctors, nurses, medical laboratory technologists, andpharmacists. Research professionals can be, for example, principleinvestigators, research technicians, postdoctoral trainees, and graduatestudents. A professional can be assisted by (1) determining whetherspecific polymorphic variants are present in a biological sample from asubject, and (2) communicating information about polymorphic variants tothat professional.

After information about specific polymorphic variants is reported, amedical professional can take one or more actions that can affectpatient care. For example, a medical professional can record informationin the patient's medical record regarding the patient's risk ofdeveloping an SSD (e.g., SZ). In some cases, a medical professional canrecord information regarding risk assessment, or otherwise transform thepatient's medical record, to reflect the patient's current medicalcondition. In some cases, a medical professional can review and evaluatea patient's entire medical record and assess multiple treatmentstrategies for clinical intervention of a patient's condition.

A medical professional can initiate or modify treatment after receivinginformation regarding a patient's diagnosis of or risk of developing anSSD (e.g., SZ), for example. In some cases, a medical professional canrecommend a change in therapy. In some cases, a medical professional canenroll a patient in a clinical trial for, by way of example, detectingcorrelations between a haplotype as described herein and any measurableor quantifiable parameter relating to the outcome of the treatment asdescribed above.

A medical professional can communicate information regarding a patient'sdiagnosis of risk of developing an SSD (e.g., SZ) to a patient or apatient's family. In some cases, a medical professional can provide apatient and/or a patient's family with information regarding an SSD(e.g., SZ) and diagnosis or risk assessment information, includingtreatment options, prognosis, and referrals to specialists. In somecases, a medical professional can provide a copy of a patient's medicalrecords to a specialist.

A research professional can apply information regarding a subject'sdiagnosis of or risk of developing an SSD (e.g., SZ) to advancescientific research. For example, a researcher can compile data on wildspecific polymorphic variants. In some cases, a research professionalcan obtain a subject's haplotype as described herein to evaluate asubject's enrollment, or continued participation, in a research study orclinical trial. In some cases, a research professional can communicateinformation regarding a subject's diagnosis of or risk of developing anSSD (e.g., SZ) to a medical professional. In some cases, a researchprofessional can refer a subject to a medical professional.

Any appropriate method can be used to communicate information to anotherperson (e.g., a professional). For example, information can be givendirectly or indirectly to a professional. For example, a laboratorytechnician can input a patient's polymorphic variant haplotype asdescribed herein into a computer-based record. In some cases,information is communicated by making an physical alteration to medicalor research records. For example, a medical professional can make apermanent notation or flag a medical record for communicating the riskassessment to other medical professionals reviewing the record. Inaddition, any type of communication can be used to communicate the riskassessment information. For example, mail, e-mail, telephone, andface-to-face interactions can be used. The information also can becommunicated to a professional by making that information electronicallyavailable to the professional. For example, the information can becommunicated to a professional by placing the information on a computerdatabase such that the professional can access the information. Inaddition, the information can be communicated to a hospital, clinic, orresearch facility serving as an agent for the professional.

Articles of Manufacture

Also provided herein are articles of manufacture comprising a probe thathybridizes with a region of human chromosome as described herein and canbe used to detect a polymorphism described herein. For example, any ofthe probes for detecting polymorphisms described herein can be combinedwith packaging material to generate articles of manufacture or kits. Thekit can include one or more other elements including: instructions foruse; and other reagents such as a label or an agent useful for attachinga label to the probe. Instructions for use can include instructions fordiagnostic applications of the probe for making a diagnosis of orassessing risk of an SSD (e.g., SZ) in a method described herein. Otherinstructions can include instructions for attaching a label to theprobe, instructions for performing in situ analysis with the probe,and/or instructions for obtaining a sample to be analyzed from asubject. In some cases, the kit can include a labeled probe thathybridizes to a region of human chromosome as described herein.

The kit can also include one or more additional reference or controlprobes that hybridize to the same chromosome or another chromosome orportion thereof that can have an abnormality associated with aparticular endophenotype. A kit that includes additional probes canfurther include labels, e.g., one or more of the same or differentlabels for the probes. In other embodiments, the additional probe orprobes provided with the kit can be a labeled probe or probes. When thekit further includes one or more additional probe or probes, the kit canfurther provide instructions for the use of the additional probe orprobes. Kits for use in self-testing can also be provided. Such testkits can include devices and instructions that a subject can use toobtain a biological sample (e.g., buccal cells, blood) without the aidof a health care provider. For example, buccal cells can be obtainedusing a buccal swab or brush, or using mouthwash.

Kits as provided herein can also include a mailer (e.g., a postage paidenvelope or mailing pack) that can be used to return the sample foranalysis, e.g., to a laboratory. The kit can include one or morecontainers for the sample, or the sample can be in a standard bloodcollection vial. The kit can also include one or more of an informedconsent form, a test requisition form, and instructions on how to usethe kit in a method described herein. Methods for using such kits arealso included herein. One or more of the forms (e.g., the testrequisition form) and the container holding the sample can be coded, forexample, with a bar code for identifying the subject who provided thesample.

Databases and Reports

Also provided herein are databases that include a list of polymorphismsas described herein, and wherein the list is largely or entirely limitedto polymorphisms identified as useful for determining a diagnosis orsusceptibility to an SSD (e.g., SZ) as described herein. The list isstored, e.g., on a flat file or computer-readable medium. The databasescan further include information regarding one or more subjects, e.g.,whether a subject is affected or unaffected, clinical information suchas endophenotype, age of onset of symptoms, any treatments administeredand outcomes (e.g., data relevant to pharmacogenomics, diagnostics ortheranostics), and other details, e.g., about the disorder in thesubject, or environmental or other genetic factors. The databases can beused to detect correlations between a particular haplotype and theinformation regarding the subject.

The methods described herein can also include the generation of reports,e.g., for use by a patient, care giver, payor, or researcher, thatinclude information regarding a subject's response allele(s), andoptionally further information such as treatments administered,treatment history, medical history, predicted response, and actualresponse. The reports can be recorded in a tangible medium, e.g., acomputer-readable disk, a solid state memory device, or an opticalstorage device.

Engineered Cells

Also provided herein are engineered cells that harbor one or morepolymorphism described herein, e.g., one or more polymorphismsassociated with an SSD (e.g., SZ), e.g., a SNP or CNV. Such cells areuseful for studying the effect of a polymorphism on physiologicalfunction, and for identifying and/or evaluating potential therapeuticagents such as anti-psychotics for the treatment of an SSD (e.g., SZ).

As one example, included herein are cells in which one of the variousalleles of the genes described herein has been re-created that isassociated with an increased risk of an SSD (e.g., SZ). Methods areknown in the art for generating cells, e.g., by homologous recombinationbetween the endogenous gene and an exogenous DNA molecule introducedinto a cell, e.g., a cell of an animal. In some cases, the cells can beused to generate transgenic animals using methods known in the art.

The cells are preferably mammalian cells (e.g., neuronal type cells) inwhich an endogenous gene has been altered to include a polymorphism asdescribed herein. Techniques such as targeted homologous recombinations,can be used to insert the heterologous DNA as described in, e.g.,Chappel, U.S. Pat. No. 5,272,071; WO 91/06667, published in May 16,1991.

EXAMPLES

The invention is further described in the following examples, which donot limit the scope of the invention described in the claims.

Example 1 Alleles Associated with Risk of Developing Schizophrenia

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE),a large federally funded clinical trial designed to assess the efficacyof antipsychotics in a real world setting, is a valuable resource fordetermining the role of genes in drug response (Stroup et al.,Schizophr. Bull. 29:15-31 (2003); Lieberman et al., N. Engl. J. Med.353:1209-1223 (2005)). As part of the CATIE trial, SNP genotyping wasperformed for roughly half of the trial participants (Sullivan et al.,Mol. Psychiatry. 13:570-584 (2008)). When combined with disease status,PANSS scores, and clinical drug response data, the genotyping dataallows the identification of genetic variants (e.g., SNPs) that arestatistically associated with specific responses to selected treatments.

The design of the CATIE study has been described in detail by others(see, e.g., Stroup et al., Schizophr. Bull. 29:15-31 (2003); Liebermanet al., N. Engl. J. Med. 353:1209-1223 (2005)). Briefly, 1460 subjectswere randomly assigned one of several antipsychotics and those who didnot respond or chose to quit their current medication were re-randomizedto another drug. Details regarding SNP genotyping and quality controlhave been recently published (Sullivan et al., Mol. Psychiatry.13:570-584 (2008)).

Genotype and phenotype data for the CATIE trial were made available toqualified researchers through the NIMH Center for Collaborative GeneticStudies on Mental Disorders. Data for 417 patients with schizophreniaand 419 unaffected controls self reported as having exclusively Europeanancestry were evaluated. This same patient population was described in arecent study by Sullivan and coworkers, which confirmed that there is nohidden stratification in the sample (Sullivan et al., Mol. Psychiatry.13:570-584 (2008)).

For the CATIE study, individual cases were diagnosed as having SZ basedon DSM-III/IV criteria.

To determine the influence of specific alleles on likelihood of havingschizophrenia, case/control association using the PLINK 1.03 wholegenome analysis toolset developed by Purcell and coworkers (Purcell etal., Am. J. Hum. Genet. 81:559-575 (2007)). For dichotomous comparisonsof affected vs. unaffected individuals, PLINK calculates P values forthe allele-specific chi-squared test and the odds ratio (OR; or relativerisk) associated with the minor allele.

Table 1 lists alleles and genotypes influencing a diagnosis of SZ. 1170SZ cases, and 1378 neurologically normal controls were used to identifythese alleles. Test 1 lists gene, SEQ ID, NCBI RS #, allele, frequencyof allele in cases, p-value, and Odds ratio for cases versus controls.

Example 2 Copy Number Variants (CNVs) that Contribute to Risk of SZ

Genotyping and phenotype data were obtained from the Genetic AnalysisInformation Network (GAIN) Database found at ncbi.nlm.nih.gov throughdbGaP, at accession number PHS000017.v1.p1. Genotypes and associatedphenotype data for the GAIN Genome-Wide Association Study ofSchizophrenia were provided by P. Gejman, and genotyping of thesesamples was provided through the Genetic Association Information Network(GAIN). Golden Helix's SVS 7.0 was used to determine the Copy NumberVariation at SNP for the genes of interest. Briefly, GAIN determine SNPand CNV variation for the samples using the Affymetrix 6.0 SNP and CNVarray. Probes were hybridized to the array and the intensity of thesignal recorded. These raw intensity values were imported into the SVSusing the import function of the program. Then CNV status was determinedusing the following protocol. For the present example, 1170 SZ patientsand 1378 neurologically normal controls were used to identify SNPS thatcan detect CNV regions influencing SZ risk.

Table 2 lists SNPs and associated genes, deletions of which alter thelikelihood of SZ diagnosis. P-values were calculated from Chi-squarevalues at each SNP. Odds Ratios were calculated by comparing thefrequency of a CNV in cases versus controls using the formula(Case_(freq) ^(*)(1−Control_(freq)))/(Control_(freq)^(*)(1−Case_(freq))).

Table 3 lists SNPs and associated genes, duplications of which eventthat alter the likelihood of SZ diagnosis. P-values were calculated fromChi-square values at each SNP. Odds Ratios were calculated by comparingthe frequency of a CNV in cases versus controls using the formula(Case_(freq)*(1−Control_(freq)))/(Control_(freq)*(1−Case_(freq))).

Other Embodiments

It is to be understood that while the invention has been described inconjunction with the detailed description thereof, the foregoingdescription is intended to illustrate and not limit the scope of theinvention, which is defined by the scope of the appended claims. Otheraspects, advantages, and modifications are within the scope of thefollowing claims.

TABLE 1 Alleles influencing likelihood of schizophrenia diagnosis GeneSeq ID NCBI RS# Allele Frequency P Odds Ratio PIK3CD 1 11121472 A 0.14560.0230000 1.40 RP1-21O18.1 2 10803343 G 0.0156 0.0324300 3.20AGBL4-C1ORF165 3 2153324 G 0.4000 0.0050950 1.33 AGBL4-C1ORF165 41934368 C 0.2900 0.0106600 1.33 AGBL4-C1ORF165 5 6667780 C 0.35970.0203800 1.27 AGBL4-C1ORF165 6 4285747 C 0.3893 0.0032690 1.35AGBL4-C1ORF165 7 3121522 A 0.3401 0.0224000 1.27 AGBL4-C1ORF165 812043418 T 0.3878 0.0058610 1.33 AGBL4-C1ORF165 9 3122291 T 0.42340.0175500 1.27 SCP2 10 7546714 T 0.1360 0.0231900 1.41 LRP8 11 5174 A0.3663 0.0044880 0.75 LRP8 12 2297660 A 0.3829 0.0112400 0.78 LRP8 132297657 A 0.3521 0.0276000 0.80 PRKACB 14 6701486 A 0.2476 0.01575001.33 PRKACB 15 2642186 G 0.2350 0.0400800 1.28 CGN 16 1573129 T 0.13650.0079840 0.70 OLFML2B 17 12025136 C 0.2792 0.0002507 1.52 DPT 181018453 C 0.5048 0.0053390 1.32 SEC16B 19 943762 A 0.0859 0.0097780 0.66SEC16B 20 4652279 A 0.0859 0.0141700 0.67 MR1 21 3845422 A 0.19330.0052410 0.72 LAMC1 22 6424888 A 0.4253 0.0024470 0.74 LAMC1 23 2274984C 0.4234 0.0032510 0.75 LAMC1 24 2027085 A 0.4246 0.0044230 0.76 KCNK225 2841598 G 0.5188 0.0000422 1.51 KCNK2 26 10779634 T 0.3484 0.00323301.36 KCNK2 27 2123331 G 0.3814 0.0351800 1.25 KCNK2 28 17024179 C 0.18590.0330100 1.33 KCNK2 29 4655272 A 0.5203 0.0144700 1.27 KCNK2 3010779647 T 0.3804 0.0095630 1.31 KCNK2 31 6684084 G 0.3123 0.04044001.25 KCNK2 32 10779651 C 0.3140 0.0453500 1.25 KCNK2 33 10494994 A0.2530 0.0196600 1.31 ESRRG 34 1984137 C 0.4332 0.0188000 0.79 ESRRG 3512037068 C 0.1745 0.0264100 1.36 ESRRG 36 12033378 A 0.1711 0.04777001.31 GNG4 37 508208 G 0.3864 0.0403200 1.23 RYR2 38 2169902 A 0.07350.0102100 0.64 RYR2 39 515474 C 0.2200 0.0237200 1.32 RYR2 40 4659819 T0.4569 0.0094780 0.78 FMN2 41 1542400 G 0.4709 0.0387700 0.82 RGS7 42191735 A 0.4294 0.0496000 1.22 PLD5 43 2036407 C 0.3254 0.0340200 1.26C2ORF46 44 182971 C 0.2746 0.0213700 1.30 C2ORF46 45 3102945 C 0.17230.0056010 1.47 C2ORF46 46 2562011 C 0.1819 0.0160100 1.38 KCNF1 471317761 A 0.3623 0.0031120 1.36 KCNF1 48 4669647 T 0.2265 0.0378100 1.29KCNF1 49 4669651 T 0.1850 0.0388100 1.32 ASXL2 50 9309437 T 0.20330.0009717 1.54 CRIM1 51 4670549 T 0.4606 0.0418900 1.22 CRIM1 52 2049367A 0.3065 0.0301000 1.27 CRIM1 53 3770876 C 0.4318 0.0374900 1.23 CRIM154 3755197 A 0.3038 0.0037720 0.74 CRIM1 55 11681392 T 0.2995 0.01252000.77 HAAO 56 3816182 A 0.2745 0.0054010 1.37 PLEKHH2 57 17414362 A0.2307 0.0038410 1.43 PRKCE 58 6732900 T 0.4522 0.0136500 1.28 PRKCE 594953270 G 0.4677 0.0307800 1.24 FBXO11 60 874869 G 0.5024 0.0275500 1.24PSME4 61 805404 C 0.2680 0.0059070 0.74 PSME4 62 10183655 T 0.38620.0364200 0.81 PSME4 63 17045488 G 0.2339 0.0055770 0.73 ACYP2 646721970 A 0.2138 0.0007330 0.68 CCDC85A 65 10460558 A 0.2709 0.00025750.68 AAK1 66 2871965 T 0.4320 0.0214300 1.26 AAK1 67 3821277 G 0.41150.0156200 1.28 AAK1 68 6546534 T 0.3067 0.0451800 1.24 AAK1 69 6712370 C0.2990 0.0170000 1.30 AAK1 70 12713679 G 0.3777 0.0048500 1.34 AAK1 7110779953 G 0.3062 0.0317300 1.26 AAK1 72 12471316 G 0.4379 0.00687801.31 CTNNA2 77 17339556 C 0.3166 0.0012970 1.43 CTNNA2 78 2861914 G0.3270 0.0042960 1.36 CTNNA2 79 2060393 A 0.4545 0.0048890 1.32 CTNNA280 17018905 C 0.0914 0.0024250 1.80 NAP5 85 10176860 C 0.2129 0.02477000.77 LRP1B 86 2171107 A 0.3043 0.0299400 1.27 LRP1B 87 10496906 A 0.36290.0014900 0.73 LRP1B 88 10183142 T 0.5291 0.0016930 1.36 LRP1B 891369542 T 0.4830 0.0064530 1.31 LRP1B 90 12623563 A 0.4149 0.01924000.79 LRP1B 91 13382235 G 0.0663 0.0081100 0.62 KYNU 92 10176234 A 0.36420.0281600 0.80 KYNU 93 6429997 C 0.3926 0.0293700 0.81 KYNU 94 3816193 A0.1981 0.0485300 1.29 KIF5C 95 4667369 C 0.3618 0.0419700 0.81 CACNB4 9613421383 T 0.1885 0.0151300 0.75 CACNB4 97 12693235 C 0.2297 0.01159000.75 FMNL2 98 2164402 G 0.2530 0.0177800 0.77 FMNL2 99 4664114 T 0.28170.0002634 0.68 FMNL2 100 17327752 A 0.2380 0.0051350 0.73 FMNL2 1012346182 G 0.3329 0.0127600 0.78 FMNL2 102 10497108 C 0.1158 0.01382000.70 FMNL2 103 10497111 A 0.1208 0.0191800 0.72 FMNL2 104 11682487 C0.3341 0.0127800 0.78 PKP4 105 2528593 A 0.3162 0.0288800 0.80 PKP4 1062711035 C 0.0660 0.0444400 0.69 SCN7A 107 11900439 A 0.3125 0.02478000.79 CERKL 108 10490688 T 0.3425 0.0315200 1.25 CERKL 109 895901 A0.3481 0.0366200 1.24 PDE1A 110 3769794 C 0.1824 0.0444500 0.78 PARD3B111 7559302 T 0.2990 0.0117400 0.77 NRP2 112 13396083 C 0.4760 0.04403001.22 PIP5K3 113 10497899 T 0.0323 0.0421200 1.95 CNTN6 115 17038701 G0.0649 0.0003231 2.43 CNTN4 116 1502582 T 0.1993 0.0214500 1.34 CNTN4117 13092590 G 0.3007 0.0109100 0.77 CNTN4 118 17194455 T 0.36590.0114200 0.78 CNTN4 119 1551997 C 0.2876 0.0179900 0.78 ITPR1 1214685803 A 0.4639 0.0456300 1.22 IRAK2 122 6804954 A 0.4294 0.01492001.28 ATP2B2 123 13100027 T 0.0785 0.0023180 0.60 ATP2B2 124 9860273 T0.0704 0.0152900 0.65 SLC6A6 125 2241780 C 0.1901 0.0316600 0.77 SLC6A6126 2304510 G 0.1432 0.0209700 0.74 DAZL 127 890640 A 0.1594 0.00066431.65 DAZL 128 4234537 C 0.1516 0.0071020 1.49 ARPP-21 129 735353 A0.4453 0.0280100 1.25 ARPP-21 130 11920715 T 0.4471 0.0414800 1.23 STAC131 17035045 T 0.2041 0.0146400 0.75 STAC 132 4678878 C 0.3556 0.02786000.80 ULK4 133 7627972 A 0.4809 0.0397100 1.22 ULK4 134 11129908 G 0.51320.0276800 1.24 ULK4 135 7618902 G 0.3037 0.0192100 1.30 ULK4 136 9878069G 0.3723 0.0496100 1.22 ULK4 137 1495696 C 0.4566 0.0449000 1.22 ZNF167138 13081859 G 0.2876 0.0395700 0.80 CACNA2D3 139 17054677 A 0.20050.0069870 1.42 FLNB 140 12632456 A 0.2852 0.0165800 1.31 FHIT 14213320646 A 0.4523 0.0019850 1.37 FHIT 143 7631246 T 0.4487 0.00342801.34 FHIT 144 9875228 T 0.1811 0.0422500 1.31 FHIT 145 1470035 A 0.44220.0075020 1.31 FHIT 146 9843007 T 0.3971 0.0209600 1.26 FHIT 147 4688167C 0.2955 0.0451000 1.25 PRICKLE2 148 17665101 G 0.1938 0.0432600 0.79ADAMTS9 149 9847307 T 0.0167 0.0073290 4.73 ADAMTS9 150 6787633 G 0.01310.0122100 5.56 MAGI1 151 7612634 C 0.5181 0.0053860 1.32 MAGI1 1527612636 G 0.5180 0.0090200 1.29 MAGI1 153 7612644 C 0.5181 0.01048001.29 FOXP1 154 2597312 C 0.3565 0.0316900 1.25 GBE1 157 2307058 T 0.31080.0168800 1.30 GBE1 158 7613144 T 0.3115 0.0203600 1.29 GBE1 159 3772891A 0.2271 0.0398500 0.79 EPHA6 160 16838196 A 0.0503 0.0304900 0.64PLCXD2 163 13074817 G 0.4112 0.0131700 0.78 PLCXD2 164 4284954 C 0.41570.0146100 0.78 PLCXD2 165 13079085 C 0.4161 0.0207800 0.80 PLCXD2 1666768713 A 0.4163 0.0312900 0.81 PLCXD2 167 12490166 A 0.4233 0.04351000.82 EPHB1 168 39704 A 0.4638 0.0343900 0.81 SPSB4 169 7620622 A 0.24520.0054850 1.40 SPSB4 170 6780365 C 0.1783 0.0007646 1.60 SPSB4 1712086180 G 0.1271 0.0018360 1.66 SERPINI2 172 4955673 C 0.5099 0.00960701.30 SERPINI2 173 17246389 C 0.2715 0.0186500 1.31 SERPINI2 174 13062550C 0.4842 0.0225700 1.25 TNIK 175 9824475 G 0.2649 0.0045900 0.74 PLD1176 187229 T 0.4171 0.0245500 1.25 PLD1 177 181715 T 0.4077 0.03434001.24 NLGN1 179 10936780 G 0.0831 0.0015080 0.60 NLGN1 180 12634066 A0.0827 0.0017380 0.60 NLGN1 181 9828801 T 0.0670 0.0140000 0.64 LEPREL1182 9835230 A 0.2226 0.0027880 0.71 LEPREL1 183 1447935 T 0.18960.0051530 0.72 LEPREL1 184 6444412 T 0.2859 0.0040510 0.74 LEPREL1 1851447936 C 0.2026 0.0104000 0.74 LEPREL1 186 7632740 C 0.3050 0.03015000.80 LEPREL1 187 1526031 C 0.2041 0.0406100 0.79 UBXD7 188 6774540 T0.4509 0.0324200 0.81 UBXD7 189 9841810 C 0.4523 0.0450600 0.82 UBXD7190 9847223 T 0.4547 0.0450800 0.82 SLC2A9 191 1568318 C 0.23390.0444200 1.27 SLC2A9 192 4697692 T 0.2124 0.0477700 1.28 SLC2A9 1933733591 A 0.1679 0.0431800 0.78 LDB2 194 157631 G 0.0728 0.0204900 0.67LDB2 195 284210 T 0.0704 0.0339900 0.69 KIAA1239 203 17575883 A 0.16500.0236800 0.75 KIAA1239 204 17575897 T 0.1699 0.0341100 0.77 UBE2K 205192779 A 0.1835 0.0004961 0.66 LIMCH1 206 6447080 G 0.4263 0.00483501.33 LIMCH1 207 6447081 G 0.4258 0.0068670 1.31 LIMCH1 208 4610372 G0.4259 0.0082180 1.31 LIMCH1 209 4861118 A 0.4195 0.0115200 1.29LOC389207 211 13105520 T 0.3474 0.0006047 0.71 LOC389207 212 9994547 A0.3507 0.0019500 0.73 LOC389207 213 1561147 G 0.2993 0.0038420 0.74 SCD5214 3897960 A 0.1791 0.0068990 0.72 SCD5 215 17352017 G 0.1325 0.03836000.75 HERC3 216 2972021 A 0.2733 0.0220900 1.30 HERC3 217 3017906 G0.2977 0.0396900 1.26 FAM13A1 218 7657817 T 0.1778 0.0187500 1.37FAM13A1 219 12507401 C 0.2175 0.0200500 1.34 COL25A1 220 9996734 A0.3973 0.0476000 1.22 ANK2 221 11942005 G 0.1555 0.0380200 1.34 CAMK2D222 11098193 T 0.2871 0.0442900 1.25 NDST3 223 6534079 A 0.21460.0433700 0.79 NDST3 224 4576085 G 0.1108 0.0017390 0.64 GPR103 22513110738 G 0.2069 0.0025070 1.48 MAML3 226 3796633 G 0.0776 0.04626000.71 IL15 227 2139383 T 0.5132 0.0274900 1.24 IL15 228 1389099 T 0.31940.0056800 0.75 IL15 229 1389098 T 0.5048 0.0315000 1.23 INPP4B 2341497389 T 0.3471 0.0057580 0.76 INPP4B 236 17715707 G 0.3026 0.02514000.79 POU4F2 240 1104532 A 0.1177 0.0004148 0.61 POU4F2 241 1394279 G0.1187 0.0004232 0.61 DCLK2 242 6535725 A 0.4542 0.0234900 1.25 FSTL5244 2082669 G 0.1953 0.0016150 1.53 FSTL5 245 6814301 T 0.3213 0.02369000.79 TLL1 246 17633393 T 0.0293 0.0080040 2.73 PALLD 247 924511 T 0.41990.0087490 1.30 PALLD 248 10033898 C 0.4939 0.0455700 1.22 CASP3 2499685847 G 0.4426 0.0108700 0.78 CASP3 250 2720376 C 0.4439 0.01462000.79 PLEKHG4B 251 6554947 G 0.3128 0.0069270 1.35 PLEKHG4B 252 17559144T 0.4545 0.0269000 1.25 AHRR 253 2721004 T 0.3075 0.0004755 1.48 AHRR254 2721012 G 0.2555 0.0012100 1.48 DNAH5 260 6554811 G 0.4010 0.01867000.79 DNAH5 261 2401810 G 0.3532 0.0186800 0.79 DNAH5 265 10513155 A0.3329 0.0023550 1.39 DNAH5 266 7709692 C 0.2094 0.0017740 0.70 DNAH5268 9885366 C 0.4390 0.0002241 1.45 DNAH5 269 1867679 T 0.4010 0.00597501.32 DNAH5 270 6896894 C 0.3969 0.0060990 1.32 DNAH5 271 16902953 G0.3178 0.0372700 1.25 DNAH5 272 9312854 C 0.3122 0.0468600 1.24 DNAH5273 339428 T 0.5240 0.0020490 1.35 DNAH5 274 339424 T 0.2446 0.01355001.34 CDH10 275 7714498 A 0.1843 0.0482000 0.79 CDH10 276 1896890 T0.2243 0.0499700 0.80 SLC45A2 277 10461928 G 0.3950 0.0260300 0.80SLC45A2 278 35389 G 0.0465 0.0188900 1.89 SLC1A3 279 1645651 A 0.36160.0172100 1.28 SLC1A3 280 3776569 G 0.4747 0.0082700 1.30 EGFLAM 2814869580 T 0.1283 0.0038730 1.59 EGFLAM 282 2589787 A 0.0837 0.03686001.50 EGFLAM 283 2434504 A 0.4580 0.0105700 1.29 EGFLAM 284 1428263 C0.2888 0.0126300 1.33 EGFLAM 285 9292705 A 0.0897 0.0015590 1.86 EGFLAM286 2731979 C 0.1607 0.0156600 1.41 ITGA2 288 7719848 A 0.2838 0.03858001.26 ELOVL7 290 4700394 T 0.5240 0.0082730 1.30 ELOVL7 291 17332824 C0.3961 0.0497500 0.82 TNPO1 292 7709640 C 0.3468 0.0000269 1.58 TNPO1293 153320 T 0.1815 0.0024290 1.51 TNPO1 294 34653 T 0.1790 0.00321201.50 TNPO1 295 266444 C 0.1766 0.0045020 1.48 TNPO1 296 2548331 A 0.42700.0001619 0.69 FCHO2 297 478575 C 0.5024 0.0001957 1.45 FCHO2 298 185435G 0.1731 0.0116100 1.42 FCHO2 299 2277017 C 0.3244 0.0417000 1.25 CMYA5300 6880680 C 0.0981 0.0160600 1.54 CMYA5 301 3828611 G 0.0740 0.01823001.64 CMYA5 302 1991483 G 0.3750 0.0384900 1.24 THBS4 303 256444 C 0.18420.0279200 1.34 THBS4 304 7736549 A 0.1496 0.0185900 1.42 VCAN 305 178024A 0.3789 0.0423000 1.23 MEF2C 306 700592 G 0.4224 0.0215300 1.26 GPR98307 16868917 G 0.0586 0.0309900 0.66 GPR98 309 2222244 A 0.37010.0473700 1.23 FBXL17 311 12519388 T 0.1940 0.0205700 1.35 FBXL17 31212189428 G 0.1902 0.0253400 1.34 FBXL17 316 7731562 C 0.1843 0.01223001.40 FBXL17 318 10515385 C 0.1850 0.0251400 1.35 FBXL17 319 11242664 G0.1795 0.0312100 1.34 PJA2 320 1045706 A 0.4221 0.0179100 1.27 PJA2 3212963046 T 0.3741 0.0295800 1.25 SNX2 322 4343835 C 0.3942 0.0015170 0.73SNX2 323 4835894 C 0.2983 0.0055500 0.75 SNX2 324 6872932 T 0.48190.0009375 1.39 SNX2 325 3822367 G 0.4795 0.0024510 1.35 SNX2 32610519715 A 0.2998 0.0078400 0.76 SNX2 327 2407403 G 0.3708 0.02282001.27 SNX24 328 27740 T 0.4832 0.0016230 1.37 SNX24 329 6888023 T 0.30140.0051010 0.75 SNX24 330 246286 T 0.3925 0.0300700 1.25 SNX24 331 246266C 0.3927 0.0378300 1.24 SNX24 332 1038078 T 0.1295 0.0318400 1.40 SNX24333 30028 C 0.3462 0.0394200 1.24 SNX24 334 385996 G 0.3584 0.04069001.24 ADAMTS19 335 30651 G 0.3628 0.0229300 1.27 TRPC7 336 950714 G0.1196 0.0005632 1.80 TRPC7 337 2649691 A 0.1446 0.0067400 1.51 CTNNA1338 906695 G 0.2718 0.0003555 0.68 CTNNA1 339 10038162 A 0.27570.0010250 0.71 CTNNA1 340 10045605 C 0.2745 0.0012850 0.71 ODZ2 3411560654 T 0.2163 0.0093960 0.74 ODZ2 342 3733988 C 0.5024 0.0169100 1.27ODZ2 343 17632540 T 0.2723 0.0285300 0.79 ODZ2 344 1422421 T 0.42720.0087630 1.30 SLC22A23 347 17136575 G 0.1651 0.0137700 0.73 RNF144B 3542038745 A 0.1539 0.0207700 0.74 RNF144B 355 1408267 G 0.2017 0.02252000.77 RNF144B 356 1324573 G 0.4189 0.0106700 0.78 RNF144B 358 1924467 T0.4077 0.0077010 1.31 RNF144B 359 9477749 C 0.4270 0.0189100 1.27RNF144B 360 9396868 T 0.1169 0.0444400 0.75 SLC17A4 361 1892248 T 0.24220.0008890 0.70 SLC17A4 362 12662869 A 0.2566 0.0001516 0.67 SLC17A1 3631575535 T 0.2421 0.0001745 0.66 SLC17A1 364 1165196 C 0.4759 0.01381001.28 SLC17A1 365 1165177 T 0.5000 0.0196400 1.26 SLC17A1 366 2070642 T0.2398 0.0006451 0.69 SLC17A1 367 4712976 T 0.2272 0.0027410 0.71SLC17A3 368 1165205 T 0.5097 0.0026860 1.35 SLC17A2 369 9467652 G 0.35530.0061210 0.76 BTN3A1 371 17610161 A 0.1310 0.0157600 1.47 BTN3A1 37210946824 G 0.1854 0.0209400 1.36 BTN2A3 373 7751280 T 0.1826 0.02904001.34 BTN2A3 374 10946829 A 0.1826 0.0290400 1.34 BTN3A3 375 3846847 T0.1818 0.0322200 1.33 BTNL2 376 2076533 A 0.4627 0.0294300 1.24 BTNL2377 3763307 T 0.3062 0.0432400 1.25 LRFN2 378 1347257 T 0.4356 0.04507000.82 ELOVL5 405 9474507 A 0.1492 0.0003639 0.63 RIMS1 408 2250128 C0.3194 0.0375900 0.80 KLHL32 409 1206084 A 0.2488 0.0006100 0.69 KLHL32410 1629523 T 0.1247 0.0062920 0.68 KLHL32 411 1737646 A 0.12530.0115400 0.70 KLHL32 412 1766518 G 0.1482 0.0207100 0.74 KLHL32 4132294763 G 0.0239 0.0161500 0.51 KLHL32 414 1206149 A 0.4964 0.04140001.22 SLC22A16 415 17071719 A 0.1043 0.0000963 2.09 SLC22A16 416 17071722T 0.1081 0.0002709 1.96 SLC22A16 417 7768422 C 0.1074 0.0004135 1.90HS3ST5 418 1334900 T 0.3952 0.0002151 1.47 TRDN 419 1570187 C 0.30460.0118000 0.77 TRDN 420 6915835 C 0.3075 0.0384000 0.80 TRDN 421 2169092T 0.3911 0.0472200 0.82 NKAIN2 422 173067 A 0.3726 0.0432500 1.23 EYA4423 9321395 A 0.2296 0.0126200 1.36 EYA4 424 9321396 G 0.2297 0.02408001.31 EYA4 425 9375953 A 0.1942 0.0297400 1.33 EYA4 426 17641157 G 0.18600.0135400 1.39 PDE7B 428 6906788 T 0.0731 0.0435000 1.52 PDE7B 4296938424 T 0.0501 0.0348800 1.71 PLAGL1 430 6916498 A 0.2315 0.03284001.29 PLAGL1 431 9484836 A 0.2307 0.0390900 1.28 UTRN 432 9496982 T0.2589 0.0330600 1.28 SYNE1 433 2252755 G 0.3732 0.0324300 1.25 SYNE1434 718527 A 0.4163 0.0067790 0.77 SYNE1 435 2763016 C 0.3365 0.04449000.81 TFB1M 436 170843 T 0.2826 0.0066610 0.75 TFB1M 437 7775163 A 0.38190.0013430 1.40 PARK2 438 12055483 T 0.3878 0.0329400 0.81 PARK2 4396924602 C 0.3974 0.0432300 0.82 PARK2 440 9355924 A 0.3786 0.01595000.79 PDE10A 441 525643 A 0.1355 0.0128200 0.71 PDE10A 442 484842 G0.1543 0.0409300 0.77 SDK1 443 663466 A 0.2002 0.0153800 0.75 SDK1 444649186 C 0.2404 0.0369700 0.79 SDK1 445 10951446 A 0.4260 0.0087200 0.77SDK1 446 4723434 G 0.5060 0.0189100 1.26 SCIN 450 702477 C 0.30290.0059970 0.75 SCIN 451 849760 C 0.3498 0.0047510 0.75 FERD3L 45811766540 C 0.2488 0.0033220 0.72 STK31 459 4722266 A 0.1723 0.00576101.47 SKAP2 460 17372780 C 0.3580 0.0096670 1.31 SKAP2 461 3801846 A0.2550 0.0031060 1.43 SKAP2 462 607099 G 0.5120 0.0098110 1.29 SKAP2 46313438514 A 0.2488 0.0056350 1.39 SKAP2 464 17315929 T 0.2458 0.00804101.37 SKAP2 465 10486483 A 0.2452 0.0122600 1.35 SKAP2 466 3801844 C0.2518 0.0033500 1.42 CREB5 467 6977628 T 0.2694 0.0174400 1.31 CREB5468 886750 A 0.2691 0.0180700 1.31 CREB5 469 10225559 C 0.2639 0.04141001.26 CHN2 470 245927 A 0.5323 0.0003594 1.42 PDE1C 471 30568 C 0.16150.0153700 1.41 PDE1C 472 30589 G 0.1289 0.0451600 1.36 PDE1C 473 30586 A0.1103 0.0101600 1.56 BMPER 474 11768532 A 0.1787 0.0104600 0.73 BMPER475 1946145 T 0.2560 0.0081850 0.75 BMPER 476 1420335 C 0.3042 0.02075000.78 EEPD1 477 11765336 G 0.5237 0.0256800 1.25 EEPD1 478 197352 C0.2753 0.0306100 0.79 VPS41 479 6462865 G 0.4044 0.0110700 0.78 VPS41480 17618395 G 0.3923 0.0167700 0.79 VPS41 481 4723793 G 0.38400.0086410 1.31 VPS41 482 3801127 G 0.5216 0.0392500 1.22 VPS41 48310085898 C 0.4510 0.0189400 0.79 VPS41 484 12532461 A 0.2500 0.01292001.34 VPS41 485 859522 G 0.0962 0.0223400 1.52 CDC2L5 486 12536726 G0.0944 0.0054230 1.69 ABCA13 490 17132335 A 0.0716 0.0243200 0.67 ABCA13491 6958356 A 0.3842 0.0416300 0.82 GRB10 492 6593182 G 0.1551 0.03084000.76 GRB10 493 4947465 C 0.1277 0.0182900 0.72 MAGI2 503 12531031 T0.1811 0.0121700 1.40 MAGI2 504 1918930 C 0.1630 0.0406500 1.33 MAGI2505 7782875 C 0.0206 0.0309200 0.52 MAGI2 506 2191806 C 0.1763 0.02347001.36 MAGI2 508 1528267 C 0.1687 0.0355400 1.34 SEMA3E 510 3801535 G0.2404 0.0092120 1.37 ABCB4 511 31671 G 0.2309 0.0022770 1.46 GTPBP10512 11972149 T 0.2258 0.0487400 1.28 PPP1R9A 521 1918482 A 0.47230.0160800 1.27 PPP1R9A 522 12690919 T 0.4395 0.0194500 0.79 PPP1R9A 523854520 T 0.4303 0.0104200 0.78 PPP1R9A 524 854535 C 0.4236 0.03569000.81 DYNC1I1 526 42066 A 0.1103 0.0002832 0.59 ZNF3 527 4424195 G 0.29020.0113800 1.33 ZNF3 528 941290 A 0.1509 0.0101000 0.71 KCND2 53917142782 G 0.0324 0.0090350 2.49 CADPS2 543 1476898 T 0.1878 0.01805001.37 CADPS2 544 2471194 A 0.1897 0.0268400 1.34 CADPS2 545 17144752 T0.1933 0.0281300 1.33 SLC13A1 546 10500090 C 0.2512 0.0003513 0.68SLC13A1 548 2140516 C 0.2709 0.0005947 0.69 EXOC4 569 12536963 G 0.30550.0186200 0.78 TBXAS1 578 12534299 G 0.4199 0.0494600 0.82 PTPRN2 59212674047 T 0.2344 0.0493700 1.26 CSMD1 598 7845140 G 0.0537 0.04190001.64 CSMD1 604 895695 G 0.5167 0.0165200 1.27 CSMD1 605 12543159 T0.4255 0.0181100 0.79 CSMD1 606 1161518 T 0.3046 0.0177000 0.78 MCPH1608 2515514 A 0.1993 0.0007415 1.56 MCPH1 609 11994063 T 0.19570.0379400 0.78 SGCZ 610 7822045 A 0.2737 0.0261500 1.29 SLC7A2 6112588233 C 0.4658 0.0074110 1.31 SLC7A2 612 2237817 C 0.3902 0.00060211.42 PSD3 613 17595783 C 0.2086 0.0252700 1.33 PSD3 614 13275817 A0.2990 0.0031010 1.39 PSD3 615 1873085 C 0.3138 0.0094100 1.33 PSD3 6161565231 T 0.4725 0.0333100 1.23 ENTPD4 627 17089269 C 0.0728 0.04101001.53 UNC5D 628 2589344 T 0.1778 0.0302100 0.77 SNTG1 629 906656 C 0.35890.0433900 1.23 SNTG1 630 11986411 G 0.3208 0.0364800 1.26 LYN 631 868541A 0.4366 0.0205200 0.79 LYN 632 17812677 T 0.2201 0.0084810 0.74 LYN 63316922508 C 0.2302 0.0171600 0.76 LYN 634 6988853 A 0.2476 0.0208000 0.77LYN 635 2668003 C 0.2464 0.0223500 0.78 PLAG1 636 7830138 C 0.18110.0090210 0.73 PLAG1 637 13273123 G 0.1627 0.0116500 0.73 NKAIN3 6421901409 C 0.3852 0.0063910 0.76 NKAIN3 643 10504354 A 0.3210 0.04496000.81 NKAIN3 644 10504356 G 0.0803 0.0076550 0.64 NKAIN3 645 10504358 G0.0800 0.0252100 0.69 DEPDC2 646 3793379 A 0.1379 0.0138700 1.46 DEPDC2647 3793381 A 0.1355 0.0311500 1.39 CRISPLD1 648 16939013 A 0.16150.0015940 0.67 CRISPLD1 649 1455795 T 0.0921 0.0321600 0.71 CRISPLD1 6507826672 T 0.2883 0.0012110 0.71 CRISPLD1 651 6472888 T 0.2739 0.00099180.71 CRISPLD1 652 16939030 C 0.1739 0.0344300 0.77 MMP16 653 2139481 T0.4081 0.0348300 1.24 BAALC 654 13279226 A 0.2542 0.0107500 0.76 ZFPM2655 13280496 C 0.3012 0.0056020 0.75 ZFPM2 656 12679854 T 0.33650.0253900 0.80 ZFPM2 657 6981187 G 0.3393 0.0296600 0.80 ZFPM2 6586469014 T 0.1775 0.0233600 1.36 ZFPM2 659 11986654 G 0.0829 0.04549001.47 CSMD3 661 1492678 T 0.5025 0.0352900 1.23 CSMD3 663 17640016 A0.2745 0.0186700 1.31 SAMD12 677 9642841 C 0.3627 0.0491000 1.23 FER1L6683 6981430 G 0.3759 0.0047760 0.75 FER1L6 684 7831422 G 0.11540.0189700 0.71 FER1L6 685 12375254 A 0.1196 0.0197900 0.72 DDEF1 69112675390 C 0.2512 0.0098780 0.75 DDEF1 692 4733776 T 0.3840 0.03078000.80 DDEF1 693 4733572 A 0.3973 0.0384400 0.81 DDEF1 694 4733788 G0.2069 0.0292300 0.78 DDEF1 695 11786705 G 0.2105 0.0377300 0.78 COL22A1701 13271565 T 0.2494 0.0266400 1.30 COL22A1 703 10104531 T 0.37260.0223300 1.27 COL22A1 704 12674962 C 0.4615 0.0233700 1.25 COL22A1 7059324496 T 0.3906 0.0209500 1.27 ZC3H3 706 4874147 A 0.3235 0.00171201.41 PIP5K1B 709 963707 G 0.3329 0.0294700 0.80 PIP5K1B 710 1414949 C0.5195 0.0205100 1.26 TRPM3 711 718447 A 0.2220 0.0377800 0.79 TMC1 7121417614 T 0.3493 0.0118900 1.30 TMC1 713 2793153 G 0.4663 0.0051150 1.32TMC1 714 2589615 A 0.4672 0.0052340 1.32 TMC1 715 1796991 G 0.19500.0420100 1.30 TMC1 716 13286194 C 0.0517 0.0086850 0.59 PCSK5 7171029034 G 0.3489 0.0285400 0.80 GNAQ 718 964423 T 0.2907 0.0443700 1.25GNAQ 719 7032206 A 0.2476 0.0197300 1.32 GNAQ 720 6560625 C 0.28610.0025030 1.41 NTRK2 721 7038866 A 0.2661 0.0426500 0.80 DIRAS2 722690232 A 0.2587 0.0229200 0.78 DIRAS2 723 1360471 C 0.2232 0.04042000.79 NFIL3 724 2440589 T 0.4654 0.0235300 1.25 FKTN 730 885954 C 0.46660.0206900 1.26 FKTN 731 17251166 C 0.3305 0.0368900 1.25 PALM2 7321535457 A 0.2804 0.0005222 1.49 PALM2 733 7849021 G 0.3216 0.00004711.57 PALM2 734 10980026 G 0.3258 0.0000760 1.54 PALM2 735 10980027 A0.3266 0.0001044 1.53 PALM2 736 17202497 A 0.3333 0.0003072 1.48 ZNF618737 4978561 T 0.3285 0.0213400 0.79 ZNF618 738 10982031 C 0.31740.0250200 0.79 ZNF618 739 4979326 A 0.3153 0.0300000 0.80 PTGS1 7431234909 G 0.1830 0.0481300 1.30 RALGPS1 744 665249 G 0.3377 0.00157201.40 RALGPS1 745 10760473 G 0.3373 0.0020180 1.39 RALGPS1 746 10819264 T0.4688 0.0276700 0.81 RALGPS1 747 13298677 G 0.2088 0.0018200 1.49RALGPS1 748 1028866 G 0.4714 0.0401800 0.82 SLC25A25 749 9695803 C0.1432 0.0342600 1.37 TSC1 750 7875558 A 0.1849 0.0035010 1.49 TSC1 7517858160 T 0.1890 0.0313800 1.33 TSC1 752 7035308 A 0.2644 0.0281600 1.29VAV2 753 10993826 T 0.1675 0.0055510 1.48 VAV2 754 2073929 G 0.16150.0137900 1.42 VAV2 755 3819500 T 0.1595 0.0178000 1.40 VAV2 756 7023551G 0.2206 0.0377700 1.29 PITRM1 757 7924157 C 0.1914 0.0075340 1.42 PRKCQ758 2387902 G 0.5012 0.0037310 1.33 PRKCQ 759 11254972 A 0.43530.0051860 0.76 PRKCQ 760 4747393 A 0.3819 0.0175000 0.79 CACNB2 76112779641 G 0.1427 0.0161900 0.73 ARMC3 762 1171136 A 0.2645 0.00895701.35 ARMC3 763 9665603 G 0.3464 0.0002269 1.49 ARMC3 764 10764367 C0.3477 0.0005803 1.45 ARMC3 765 1054052 T 0.3218 0.0226200 1.28 ARMC3766 12252340 T 0.2215 0.0334200 1.30 ARMC3 767 1382580 G 0.13960.0389300 1.36 ARMC3 768 1382579 G 0.0470 0.0357500 1.74 JMJD1C 77412355784 A 0.4467 0.0067450 0.77 JMJD1C 775 3999089 C 0.4450 0.00707400.77 CDH23 776 17635709 T 0.2038 0.0493200 0.79 KCNMA1 778 4639876 T0.3353 0.0200300 1.28 SORCS3 779 902300 T 0.2764 0.0218900 1.30 VTI1A780 7088500 C 0.3103 0.0006779 1.45 VTI1A 781 7907361 C 0.2962 0.00119701.44 VTI1A 782 7096151 A 0.3055 0.0021240 1.40 VTI1A 783 7070850 G0.3067 0.0451800 1.24 VTI1A 784 6585184 A 0.3390 0.0499900 1.23 ATRNL1785 2068463 C 0.4153 0.0452900 1.22 HSPA12A 786 3010460 C 0.36120.0179500 1.28 STIM1 798 2959068 T 0.4258 0.0093460 0.77 STIM1 79912803023 G 0.4569 0.0028360 0.75 TRIM21 800 1426378 A 0.1524 0.00996301.46 GALNTL4 801 4910288 A 0.3890 0.0198900 0.79 GALNTL4 802 4910289 C0.2578 0.0137900 0.77 GALNTL4 803 10831565 A 0.4672 0.0100100 1.29 SPON1804 2174146 T 0.2243 0.0357900 1.29 SPON1 805 11238 T 0.2852 0.00351200.74 IGSF22 815 4537730 A 0.2407 0.0041330 0.73 IGSF22 816 7125943 T0.2206 0.0059280 0.73 IGSF22 817 10766494 C 0.2255 0.0102600 0.75C11ORF49 818 4548577 T 0.2410 0.0178300 1.33 C11ORF49 819 11039112 T0.3433 0.0037250 1.36 C11ORF49 820 747650 A 0.3437 0.0041950 1.36 DLG2821 2507850 A 0.3353 0.0039160 0.75 DLG2 822 7108874 T 0.2524 0.01063000.76 DLG2 823 10898133 A 0.3624 0.0456200 0.82 DLG2 827 2514147 G 0.10640.0098870 1.57 DLG2 828 1943708 C 0.3527 0.0046480 1.35 DLG2 829 1943701G 0.5252 0.0095020 1.29 DLG2 830 2187359 A 0.3398 0.0243200 1.27 DLG2831 11234201 T 0.4075 0.0341200 0.81 ELMOD1 832 684901 T 0.31410.0002093 1.51 OPCML 833 10894536 A 0.0823 0.0049550 0.63 TSPAN9 83710774140 C 0.3126 0.0416600 0.81 STYK1 838 1078437 G 0.4050 0.00822901.31 STYK1 839 7350597 A 0.4647 0.0009245 1.39 STYK1 840 10845198 T0.4050 0.0223300 1.26 STYK1 841 10743918 C 0.3533 0.0466500 0.82LOC729025 842 1624759 G 0.2975 0.0448900 1.25 LRP1 843 1800176 T 0.27600.0040280 0.74 LRP1 844 1800168 C 0.2816 0.0075630 0.75 CNOT2 8451595410 C 0.4129 0.0488400 0.82 CNOT2 846 3817487 A 0.3969 0.04583000.82 KCNC2 847 2136036 G 0.3333 0.0396900 0.81 NAV3 848 7139116 C 0.13190.0173000 0.72 NAV3 849 10777655 A 0.1313 0.0243500 0.73 GAS2L3 85017030333 T 0.0431 0.0009065 2.84 SLC46A3 853 9579226 T 0.3534 0.01425000.78 SLC46A3 854 7339280 A 0.4234 0.0027410 0.75 SLC46A3 855 715704 G0.4141 0.0451800 1.22 UBL3 856 7328052 A 0.1039 0.0234600 1.49 N4BP2L2857 208431 G 0.2160 0.0064940 0.73 NBEA 858 7320580 G 0.2337 0.02493001.31 NBEA 859 7988705 A 0.2265 0.0481900 1.27 NBEA 860 17769661 T 0.14830.0490100 1.33 SLAIN1 861 1343911 A 0.1775 0.0061900 1.46 GPC5 86210851317 A 0.4604 0.0068410 1.31 GPC5 863 1330469 T 0.4486 0.03192000.81 GPC5 864 9515990 C 0.3796 0.0288700 1.25 GPC6 865 9561427 G 0.30050.0154800 1.31 GPC6 866 9589816 A 0.4012 0.0160400 1.28 NALCN 86716958230 G 0.0692 0.0074300 0.63 NALCN 868 625331 C 0.1292 0.00618700.69 ITGBL1 869 4400915 T 0.0653 0.0362700 1.60 WDR23 870 3825584 T0.3134 0.0020680 1.40 WDR23 871 11574503 C 0.3505 0.0103900 1.31 GNG2874 2357247 C 0.3589 0.0066230 0.76 GNG2 875 1959518 C 0.3969 0.00662700.76 SAMD4A 876 709939 C 0.4246 0.0123600 0.78 SAMD4A 877 8021957 T0.4224 0.0069810 0.77 SAMD4A 878 8021151 G 0.4115 0.0070300 0.77 PPP2R5E880 1255741 A 0.3301 0.0386300 1.25 RGS6 882 2239268 C 0.2760 0.00761300.75 RGS6 883 12885938 C 0.2754 0.0076460 0.75 KCNK10 886 11625905 T0.2098 0.0181400 0.76 KCNK13 887 11621045 G 0.4200 0.0029250 1.35 KCNK13888 11159957 G 0.4209 0.0043360 1.33 PSMC1 889 7150093 A 0.41790.0038340 1.34 PSMC1 890 6575120 G 0.4123 0.0050780 1.33 PSMC1 8912236403 T 0.4118 0.0060210 1.33 RPS6KA5 892 1286264 C 0.3699 0.01266000.78 RPS6KA5 893 941847 T 0.2524 0.0237800 1.31 RPS6KA5 894 1286060 C0.2691 0.0119300 1.33 RPS6KA5 895 9944098 T 0.5193 0.0264300 1.25RPS6KA5 896 7156252 T 0.3184 0.0059240 1.35 RPS6KA5 897 11159988 C0.3186 0.0065270 1.34 RPS6KA5 898 7492628 G 0.3423 0.0222200 1.28CCDC88C 901 8015982 C 0.2566 0.0043250 1.40 CCDC88C 902 10131741 G0.2542 0.0082870 1.36 CCDC88C 903 8007791 A 0.2536 0.0099850 1.35 BCL11B904 2793321 T 0.3254 0.0009968 1.43 BCL11B 905 1257446 C 0.31410.0005659 1.46 BCL11B 906 1257416 G 0.3529 0.0128600 1.30 ATP10A 9074906747 G 0.0719 0.0298000 0.68 ATP10A 908 17667563 A 0.1947 0.03505001.32 C15ORF41 909 1990659 A 0.3301 0.0255100 0.80 GLDN 910 2470172 C0.4440 0.0116100 1.29 GLDN 911 2470173 T 0.2074 0.0137300 1.37 GLDN 91216964319 T 0.0385 0.0182600 2.05 GLDN 913 10163098 G 0.0349 0.03179001.97 CLK3 914 11072496 T 0.1695 0.0067190 1.46 CLK3 915 7161903 G 0.16750.0088530 1.44 TBC1D2B 916 16969397 T 0.0933 0.0019920 1.81 TBC1D2B 9178030999 G 0.1295 0.0021610 1.64 PCSK6 918 11247300 A 0.1527 0.00732801.48 PCSK6 919 735504 C 0.4748 0.0495100 0.82 A2BP1 920 9935875 G 0.42070.0444500 0.82 A2BP1 922 1034971 G 0.3708 0.0348400 0.81 TMC5 9238058400 C 0.2434 0.0489700 1.26 TMC5 924 8063463 G 0.1954 0.0000370 1.76TMC5 925 2856608 G 0.3055 0.0040570 1.37 TMC5 926 11640077 G 0.30340.0038910 1.38 GDE1 927 739639 C 0.3926 0.0128300 1.29 GDE1 928 3751821T 0.0962 0.0098070 1.61 HYDIN 929 9939485 G 0.4475 0.0004328 0.71 HYDIN930 9939194 T 0.3664 0.0012840 1.40 HYDIN 931 184647 C 0.3522 0.03176000.80 WWOX 933 11648121 A 0.1791 0.0043000 0.71 WWOX 934 12924899 C0.2494 0.0315300 0.79 WWOX 935 7204203 A 0.0354 0.0466200 1.86 MPHOSPH6936 11150443 C 0.1265 0.0000856 1.97 MPHOSPH6 937 10514533 C 0.14920.0003630 1.72 MPHOSPH6 938 1862820 G 0.3819 0.0188200 1.27 MPHOSPH6 939918763 C 0.4904 0.0009759 1.38 MPHOSPH6 940 902542 A 0.1679 0.00005791.80 MPHOSPH6 941 2967337 C 0.1408 0.0000754 1.88 MPHOSPH6 942 2967333 G0.1667 0.0000047 2.00 MPHOSPH6 943 2967328 C 0.1663 0.0001142 1.76 CDH13944 4598906 T 0.3449 0.0296400 0.80 USP10 947 964453 G 0.2739 0.01492001.32 DNAH9 948 11650055 T 0.4511 0.0110200 0.78 DNAH9 949 7213187 G0.4463 0.0039930 1.33 RAB11FIP4 950 757378 T 0.4111 0.0069170 1.32 CA10952 11652641 G 0.2041 0.0441000 1.29 HRNBP3 953 7212305 A 0.12080.0238800 1.44 ZFP161 954 990072 T 0.4275 0.0000163 0.65 ZFP161 95511665417 T 0.4344 0.0030090 1.35 ZFP161 956 9945680 A 0.4354 0.00379801.34 ZFP161 957 9965501 T 0.0275 0.0069490 2.91 ZFP161 958 8082898 G0.0191 0.0318600 2.70 PTPRM 959 8089695 C 0.0801 0.0492000 1.47 PTPRM960 1866854 G 0.3229 0.0031190 1.38 PTPRM 961 10513901 A 0.49280.0390600 1.23 KIAA0802 962 17407982 C 0.2200 0.0023400 0.71 KIAA0802963 17408213 T 0.2159 0.0026080 0.71 OSBPL1A 964 275875 G 0.42570.0078430 0.77 CHST9 965 559547 T 0.3413 0.0086020 0.77 CHST9 96612604227 G 0.3828 0.0291900 0.80 CHST9 967 8084423 A 0.4535 0.02611001.25 CHST9 968 1426879 C 0.3205 0.0033150 1.38 CHST9 969 4800797 G0.3216 0.0039910 1.37 NEDD4L 970 4940385 C 0.4057 0.0265100 0.80 NEDD4L971 7242486 G 0.4115 0.0400400 0.81 NEDD4L 972 17064977 C 0.25420.0401800 0.80 NEDD4L 973 11152073 A 0.2542 0.0424300 0.80 CCBE1 97417065761 C 0.0979 0.0433000 0.73 CCBE1 975 12969965 A 0.2017 0.02122001.34 CDH7 977 7228669 T 0.3065 0.0427800 1.25 CDH7 978 2628210 G 0.21410.0092920 0.74 CDH7 979 2587427 A 0.3317 0.0249700 0.80 CDH7 980 2587428T 0.2811 0.0063980 0.75 TXNDC10 981 309242 G 0.1506 0.0000764 1.84FERMT1 983 6516104 T 0.1229 0.0002756 1.85 FERMT1 984 16991866 C 0.11930.0005018 1.81 PLCB1 985 6055513 G 0.4435 0.0060730 0.76 PLCB4 9866056653 G 0.1411 0.0384900 0.76 MACROD2 987 6079910 C 0.1085 0.00087391.83 MACROD2 988 6043402 A 0.0627 0.0474900 1.56 MACROD2 989 463020 G0.4248 0.0060440 0.76 MACROD2 990 6135667 T 0.3305 0.0463400 0.82 KIF16B991 6044051 T 0.1803 0.0000708 1.76 KIF16B 992 720592 T 0.3138 0.04419001.24 MAPRE1 993 410488 A 0.3959 0.0021780 0.74 MAPRE1 994 242529 C0.3353 0.0006392 1.44 ZSWIM3 996 1967656 A 0.4640 0.0035740 1.34 ZSWIM3997 6514065 C 0.4104 0.0033630 1.35 ZSWIM3 998 1045493 G 0.43150.0471300 1.22 SNAI1 999 6020157 A 0.1468 0.0298400 0.75 SNAI1 100016995010 C 0.1147 0.0150300 0.70 SNAI1 1001 6091080 G 0.1727 0.00033090.65 SNAI1 1002 6020187 G 0.2064 0.0017860 0.70 C21ORF37 1005 12483129 C0.4519 0.0044570 0.76 C21ORF37 1006 2824301 A 0.5167 0.0004203 1.41NCAM2 1007 9979231 G 0.2644 0.0095300 1.35 PDE9A 1011 2284976 A 0.38460.0019000 1.38 ARVCF 1012 2239395 G 0.0322 0.0229700 0.57 ARVCF 101312171109 A 0.1993 0.0448300 0.79 SGSM1 1014 5760752 C 0.3182 0.02996001.26 ASPHD2 1015 8140344 A 0.4951 0.0038120 1.33 ASPHD2 1016 6005042 A0.4550 0.0041750 0.75 ASPHD2 1017 6519650 C 0.3373 0.0003330 0.70 HPS41018 5761552 T 0.4507 0.0000837 0.68 ARFGAP3 1019 1018448 A 0.42460.0077450 0.77 ARFGAP3 1020 6002963 G 0.4272 0.0302100 0.81 TTLL1 10211052160 T 0.3245 0.0088850 1.33 TTLL1 1022 135002 C 0.4725 0.00791101.30 EFCAB6 1023 137794 A 0.1067 0.0406800 0.74 EFCAB6 1024 5764310 C0.0863 0.0318600 0.71 RIBC2 1025 6007043 C 0.1683 0.0004614 0.65

TABLE 2 CNV Deletions Influencing Schizophrenia Risk Gene Seq ID NCBIRS# P Odds Ratio CTNNA2 81 1930 0.020961 7.99 CTNNA2 82 101700200.039020 6.85 CTNNA2 83 6743980 0.032919 >4.00 CTNNA2 84 134231410.043911 2.45 DNER 114 6436860 0.032919 >4.00 ITPR1 120 3792490 0.021448<0.17 ROBO1 155 1457659 0.031601 0.14 ROBO1 156 3821603 0.031601 0.14KCNIP4 196 7694587 0.050947 0.58 STIM2 197 4557250 0.033306 0.58 STIM2198 4532223 0.033306 0.58 STIM2 199 4274829 0.033306 0.58 STIM2 2004692128 0.013672 0.43 STIM2 201 7671671 0.021696 0.36 INPP4B 230 31024390.035939 <0.20 INPP4B 231 1907119 0.035939 <0.20 INPP4B 232 26366450.021448 <0.17 INPP4B 235 881611 0.030163 2.98 INPP4B 239 170161750.010488 0.26 FSTL5 243 7690342 0.037009 0.28 DNAH5 257 68766730.032919 >4.00 DNAH5 258 3777093 0.032919 >4.00 DNAH5 259 65548080.032919 >4.00 DNAH5 262 7715811 0.008964 >6.00 DNAH5 263 105131530.008964 >6.00 DNAH5 264 10039621 0.050044 3.43 DNAH5 267 68743490.019794 5.14 DNAH5 268 9885366 0.019794 5.14 FBXL17 313 288180 0.0024200.44 FBXL17 314 288173 0.000172 0.22 FBXL17 317 288146 0.035939 <0.20JARID2 348 4085876 0.021448 <0.17 JARID2 349 2282827 0.035939 <0.20ELOVL5 379 10948744 0.008060 0.81 ELOVL5 380 2562898 0.009014 0.81ELOVL5 381 735860 0.007927 0.81 ELOVL5 382 2057024 0.007927 0.81 ELOVL5383 1429146 0.006239 0.80 ELOVL5 384 2073040 0.006239 0.80 ELOVL5 3859463895 0.006239 0.80 ELOVL5 386 2235723 0.007090 0.81 ELOVL5 3871346603 0.007090 0.81 ELOVL5 388 9474476 0.007090 0.81 ELOVL5 3892294867 0.007090 0.81 ELOVL5 390 9349660 0.007090 0.81 ELOVL5 391 9743230.007090 0.81 ELOVL5 392 6909592 0.006239 0.80 ELOVL5 393 93675200.006239 0.80 ELOVL5 394 9395854 0.007090 0.81 ELOVL5 395 2094850.007090 0.81 ELOVL5 396 9395856 0.009860 0.81 ELOVL5 397 77479260.010371 0.81 ELOVL5 398 7738788 0.010371 0.81 ELOVL5 399 2095000.009167 0.81 ELOVL5 400 9357760 0.009167 0.81 ELOVL5 401 93701960.005869 0.80 ELOVL5 402 209517 0.003217 0.79 ELOVL5 403 93702010.003217 0.79 ELOVL5 404 1579454 0.003217 0.79 ELOVL5 405 94745070.004235 0.80 ELOVL5 406 9296711 0.004235 0.80 ELOVL5 407 14291430.005342 0.80 NXPH1 447 2107280 0.032919 >4.00 NXPH1 448 100857200.028460 1.78 NXPH1 449 4455737 0.028460 1.78 DGKB 452 17168091 0.0250561.73 DGKB 453 6972310 0.033501 1.69 DGKB 454 12699619 0.035939 0.32 DGKB455 10499441 0.035939 0.32 CALN1 498 11768892 0.034094 0.35 CALN1 4991914381 0.034094 0.35 MAGI2 502 12670134 0.022848 0.21 PPP1R9A 51310252856 0.008106 1.28 PPP1R9A 514 6465448 0.028295 1.38 PPP1R9A 515854717 0.020137 1.29 PPP1R9A 516 854737 0.006379 0.70 PPP1R9A 5176961415 0.002304 0.70 PPP1R9A 518 17305991 0.020961 1.31 PPP1R9A 52011762113 0.008914 0.73 PPP1R9A 523 854520 0.001873 1.50 NRCAM 532 4015730.039482 0.70 NRCAM 535 422011 0.014469 0.74 NRCAM 536 425013 0.0229801.33 KCND2 542 9886190 0.019235 1.41 SLC13A1 547 12706494 0.028960 0.78SLC13A1 549 2222514 0.004704 1.55 SLC13A1 550 2402637 0.044434 0.82 GRM8556 2299500 0.028131 1.39 GRM8 560 13240418 0.031601 0.80 GRM8 5614731330 0.010313 0.70 GRM8 562 2299523 0.048865 0.79 GRM8 563 21881870.026857 1.60 GRM8 564 4141415 0.040424 1.38 GRM8 565 10226889 0.0491570.72 DGKI 572 4732255 0.015055 1.27 DGKI 576 7781327 0.046318 1.27CNTNAP2 580 10261766 0.016489 0.79 CNTNAP2 581 13228526 0.023788 1.57CNTNAP2 588 17417154 0.013828 1.49 CNTNAP2 589 1637845 0.026091 1.96PTPRN2 591 221247 0.045231 1.91 PTPRN2 593 11767654 0.023113 1.34 PTPRN2594 10231253 0.023113 0.33 PTPRN2 595 7789111 0.021448 2.30 CSMD1 597341724 0.001131 0.62 CSMD1 599 7001551 0.005054 1.79 CSMD1 601 78192250.043394 0.84 PSD3 617 4298523 0.010548 1.83 PSD3 618 2634435 0.0254941.62 PSD3 619 6987039 0.002996 1.63 PSD3 621 10106032 0.025791 0.61 PSD3625 11778310 0.016210 1.65 TOX 640 12115074 0.046871 1.27 TOX 64116924623 0.017555 1.29 CSMD3 662 1873746 0.042883 0.80 CSMD3 66512676848 0.000006 2.32 CSMD3 666 2123489 0.020022 1.48 CSMD3 66710505174 0.026242 1.44 CSMD3 669 17602393 0.022717 0.70 CSMD3 67112545742 0.048865 0.84 CSMD3 673 6999348 0.045500 0.74 CSMD3 675 14029440.033501 1.39 SAMD12 676 4631494 0.032347 1.32 SAMD12 678 92975870.002542 1.52 SAMD12 679 10955887 0.001095 1.65 SAMD12 681 25145910.005492 1.40 SAMD12 682 2514602 0.044434 1.54 MTSS1 686 38290370.009696 1.29 MTSS1 687 4871517 0.047432 0.81 MTSS1 688 919544 0.0149700.79 KCNQ3 697 2469625 0.009805 4.58 KCNQ3 698 2436134 0.019794 5.14COL22A1 702 7842696 0.009167 0.17 SMARCA2 707 16937123 0.005167 2.76FKTN 725 1858744 0.041881 0.85 FKTN 726 2768294 0.034094 0.84 FKTN 72717309806 0.031054 0.84 FKTN 728 2518106 0.031418 0.84 FKTN 729 18587430.025940 0.84 FKTN 730 885954 0.018800 0.83 FKTN 731 17251166 0.0151410.82 ASTN2 740 7032028 0.006102 10.30 CDK5RAP2 742 10760103 0.0488652.74 MYO3A 770 10764597 0.012993 <0.14 JMJD1C 772 10761739 0.035939<0.20 JMJD1C 773 10761741 0.021448 <0.17 ATE1 788 112001070.032919 >4.00 ATE1 790 11818001 0.035106 4.57 ATE1 791 107328240.035106 4.57 ATE1 792 10510101 0.019794 5.14 ATE1 793 10788221 0.0197945.14 ATE1 794 3750835 0.019794 5.14 ATE1 795 11200257 0.035106 4.57 ATE1796 11200260 0.035106 4.57 ATE1 797 11200267 0.035106 4.57 USH1C 8062072230 0.045500 0.40 USH1C 808 1076311 0.039715 0.80 USH1C 809 21904530.039715 0.80 USH1C 810 2190454 0.037446 0.79 USH1C 812 7113935 0.0098050.45 USH1C 813 7106302 0.009375 0.48 USH1C 814 2073582 0.005082 0.45DLG2 825 6592142 0.037667 0.66 DLG2 826 1914203 0.021448 <0.17 TSPAN9834 10848784 0.020961 7.99 NPAS3 872 8022434 0.017062 >5.00 NPAS3 87311851667 0.019457 0.13 PPP2R5E 879 6573522 0.011095 5.72 RGS6 88112586947 0.011221 2.95 RGS6 882 2239268 0.011221 2.95 RGS6 885 21395940.012632 0.74 CCDC88C 899 4900075 0.035106 4.57 A2BP1 921 74044220.034094 0.35 WWOX 932 16947095 0.006102 10.30 CDH13 945 20616290.012280 0.43 CCBE1 976 1864307 0.035939 <0.20 BMP7 1003 21807820.004756 >7.00

TABLE 3 CNV Duplications Influencing Schizophrenia Risk Gene Seq ID NCBIRS# P Odds Ratio CTNNA2 73 10189345 0.032919 >4.00 CTNNA2 74 37959940.017062 >5.00 CTNNA2 75 7571658 0.020961 7.99 CTNNA2 76 67415630.048865 2.74 FHIT 141 2205353 0.050044 3.43 CBLB 161 12497428 0.0292983.81 CBLB 162 6795961 0.029298 3.81 NLGN1 178 1553122 0.017062 >5.00STIM2 202 725981 0.020961 7.99 LIMCH1 210 13113314 0.012993 <0.14 INPP4B233 2635429 0.035939 <0.20 INPP4B 237 1391099 0.016965 0.45 INPP4B 2389308152 0.050947 0.52 CTNND2 255 6885224 0.035939 <0.20 CTNND2 2562190989 0.039020 6.85 DNAH5 269 1867679 0.048865 2.74 ITGA1 287 168762700.039020 6.85 PDE4D 289 35285 0.021448 <0.17 GPR98 308 10043564 0.0249122.42 GPR98 310 1852731 0.006102 10.30 FBXL17 315 288172 0.020961 7.99FBXL17 317 288146 0.011095 5.72 SERPINB6 345 7751676 0.042630 1.17SFRPINB6 346 1358869 0.020722 1.20 JARID2 350 9396591 0.032919 >4.00ATXN1 351 2237166 0.032919 >4.00 ATXN1 352 720006 0.032919 >4.00 ATXN1353 2237165 0.032919 >4.00 RNF144B 357 577287 0.003455 0.37 BTN3A1 3704712986 0.045500 0.40 PDE7B 427 9385740 0.002963 <0.10 DGKB 456 13677800.020961 7.99 DGKB 457 1431538 0.017062 >5.00 ABCA13 487 119838830.000125 0.28 ABCA13 488 2117089 0.000814 0.33 ABCA13 489 77780200.032919 >4.00 WBSCR17 494 12538186 0.039020 6.85 WBSCR17 495 6484150.032919 >4.00 CALN1 496 12673109 0.023516 3.43 CALN1 497 102601830.023113 0.33 CALN1 500 17503400 0.000270 0.06 MAGI2 501 78107780.011095 5.72 MAGI2 507 10255710 0.032919 >4.00 MAGI2 509 77787070.021448 <0.17 PPP1R9A 515 854717 0.005869 1.48 PPP1R9A 519 78063040.024484 0.65 PPP1R9A 520 11762113 0.047432 0.74 PPP1R9A 521 19184820.019794 1.49 PPP1R9A 523 854520 0.001989 1.75 PPP1R9A 525 8545370.013672 1.82 NRCAM 529 409797 0.048286 1.87 NRCAM 530 449514 0.0104881.26 NRCAM 531 107589 0.026394 0.74 NRCAM 533 404287 0.037227 1.22 NRCAM534 369800 0.002931 1.28 NRCAM 535 422011 0.002775 2.38 NRCAM 53713236767 0.016965 0.70 NRCAM 538 2284290 0.003878 1.74 KCND2 54012111791 0.002656 1.50 KCND2 541 10224891 0.006170 1.45 SLC13A1 5502402637 0.019907 1.37 GRM8 551 2299449 0.008864 1.66 GRM8 552 22377350.024064 2.20 GRM8 553 9942681 0.024064 1.21 GRM8 554 1074728 0.0471511.61 GRM8 555 886176 0.021203 1.54 GRM8 557 10487459 0.013291 1.42 GRM8558 1419508 0.000007 1.78 GRM8 559 2023735 0.012280 1.87 GRM8 56510226889 0.024064 1.75 EXOC4 566 1149550 0.040186 1.38 EXOC4 567 77832170.048865 2.74 EXOC4 568 10488164 0.005492 1.40 EXOC4 570 69664030.035313 2.10 DGKI 571 2278829 0.002979 2.09 DGKI 572 4732255 0.0140651.32 DGKI 573 4728415 0.002996 1.69 DGKI 574 1731913 0.030163 1.28 DGKI575 2113578 0.008060 2.08 DGKI 577 706561 0.018481 3.21 CNTNAP2 57917480133 0.031601 1.43 CNTNAP2 582 1548743 0.032919 0.74 CNTNAP2 5837802708 0.000396 >11.00 CNTNAP2 584 2022226 0.002715 1.66 CNTNAP2 5852373133 0.009696 2.11 CNTNAP2 586 10270551 0.000003 0.59 CNTNAP2 5876953679 0.041389 1.81 PTPRN2 590 221242 0.004098 0.72 PTPRN2 59610081235 0.025940 0.69 CSMD1 597 341724 0.028960 0.75 CSMD1 600 7503180.024203 1.86 CSMD1 602 13254344 0.006136 2.62 CSMD1 603 895696 0.0073721.65 CSMD1 607 17066296 0.001131 0.52 PSD3 620 13259762 0.010141 1.27PSD3 622 747555 0.012006 1.55 PSD3 623 7007413 0.013518 1.57 PSD3 6246993404 0.018693 1.43 PSD3 625 11778310 0.001389 2.01 PSD3 626 15068940.009805 4.58 TOX 638 7845800 0.008151 1.85 TOX 639 4738732 0.0212031.62 CSMD3 660 10505182 0.044171 0.71 CSMD3 664 6994009 0.000010 2.13CSMD3 665 12676848 0.048865 2.74 CSMD3 668 1021876 0.047715 1.39 CSMD3670 964764 0.000229 1.94 CSMD3 672 11995656 0.024064 2.20 CSMD3 67412680523 0.034094 0.72 SAMD12 677 9642841 0.000002 1.86 SAMD12 68012541916 0.008016 2.65 SAMD12 681 2514591 0.004053 3.90 SAMD12 6822514602 0.004500 1.57 MTSS1 686 3829037 0.033501 0.73 MTSS1 689 109561920.029298 2.05 MTSS1 690 6470263 0.040186 0.64 KCNQ3 696 9779390.017062 >5.00 KCNQ3 697 2469625 0.002542 >8.00 KCNQ3 699 78325890.035939 <0.20 KCNQ3 700 1379582 0.035939 <0.20 SMARCA2 708 109651130.035106 4.57 CDK5RAP2 741 914617 0.034294 1.94 MYO3A 769 127738560.035939 <0.20 ANK3 771 4948254 0.011284 9.14 KCNMA1 777 25693600.035939 <0.2 GRK5 787 10787948 0.019794 5.14 ATE1 789 753455 0.0292982.05 USH1C 807 7104083 0.013141 1.66 USH1C 808 1076311 0.006344 1.71USH1C 809 2190453 0.003455 1.77 USH1C 810 2190454 0.016677 1.64 USH1C811 17714673 0.020961 7.99 DLG2 824 6592141 0.032919 >4.00 TSPAN9 83510848789 0.004756 >7.00 TSPAN9 836 7969363 0.048865 2.74 MTIF3 8513759434 0.000181 6.05 MTIF3 852 3759433 0.001194 4.03 RGS6 884 1496410.021448 <0.17 CCDC88C 900 747159 0.035106 4.57 CDH13 946 4514340.011284 9.14 CA10 951 9303589 0.035939 <0.20 ATRN 982 6076524 0.0008770.22 PTPRT 995 6016664 0.008964 >6.00 CDH4 1004 4812313 0.034495 0.55NCAM2 1008 13052286 0.032919 >4.00 NCAM2 1009 2826815 0.029298 3.81NCAM2 1010 232509 0.050044 3.43

TABLE A Summary of SNPs (NCBI Human Genome Reference Assembly Build36.3) Seq ID Gene Chr Position Seq ID Gene Chr Position 1 PIK3CD 19,655,808 2 RP1-21O18.1 1 15,265,882 3 AGBL4-C1ORF165 1 49,012,555 4AGBL4-C1ORF165 1 49,046,634 5 AGBL4-C1ORF165 1 49,107,917 6AGBL4-C1ORF165 1 49,124,764 7 AGBL4-C1ORF165 1 49,132,460 8AGBL4-C1ORF165 1 49,133,207 9 AGBL4-C1ORF165 1 49,214,610 10 SCP2 153,261,152 11 LRP8 1 53,485,315 12 LRP8 1 53,504,903 13 LRP8 153,519,183 14 PRKACB 1 84,323,437 15 PRKACB 1 84,343,593 16 CGN 1149,764,000 17 OLFML2B 1 160,247,126 18 DPT 1 166,964,218 19 SEC16B 1176,175,475 20 SEC16B 1 176,178,830 21 MR1 1 179,279,594 22 LAMC1 1181,352,319 23 LAMC1 1 181,374,069 24 LAMC1 1 181,375,234 25 KCNK2 1213,267,433 26 KCNK2 1 213,269,771 27 KCNK2 1 213,286,968 28 KCNK2 1213,304,166 29 KCNK2 1 213,312,765 30 KCNK2 1 213,393,108 31 KCNK2 1213,405,685 32 KCNK2 1 213,412,561 33 KCNK2 1 213,428,830 34 ESRRG 1214,811,868 35 ESRRG 1 214,951,990 36 ESRRG 1 214,952,115 37 GNG4 1233,794,439 38 RYR2 1 235,793,994 39 RYR2 1 235,885,637 40 RYR2 1236,061,906 41 FMN2 1 238,512,719 42 RGS7 1 239,145,433 43 PLD5 1240,426,890 44 C2ORF46 2 8,321,006 45 C2ORF46 2 8,354,700 46 C2ORF46 28,355,126 47 KCNF1 2 10,948,881 48 KCNF1 2 10,981,799 49 KCNF1 210,999,213 50 ASXL2 2 25,956,101 51 CRIM1 2 36,467,658 52 CRIM1 236,521,723 53 CRIM1 2 36,532,532 54 CRIM1 2 36,610,853 55 CRIM1 236,611,604 56 HAAO 2 42,869,208 57 PLEKHH2 2 43,822,986 58 PRKCE 245,919,740 59 PRKCE 2 45,927,156 60 FBXO11 2 47,947,841 61 PSME4 253,970,304 62 PSME4 2 54,064,285 63 PSME4 2 54,136,333 64 ACYP2 254,201,406 65 CCDC85A 2 56,425,867 66 AAK1 2 69,604,707 67 AAK1 269,637,782 68 AAK1 2 69,650,512 69 AAK1 2 69,708,598 70 AAK1 269,716,927 71 AAK1 2 69,740,261 72 AAK1 2 69,768,980 73 CTNNA2 279,724,263 74 CTNNA2 2 79,726,512 75 CTNNA2 2 79,728,810 76 CTNNA2 279,734,051 77 CTNNA2 2 79,931,793 78 CTNNA2 2 79,934,690 79 CTNNA2 279,942,001 80 CTNNA2 2 80,337,745 81 CTNNA2 2 80,368,183 82 CTNNA2 280,373,325 83 CTNNA2 2 80,377,211 84 CTNNA2 2 80,624,319 85 NAP5 2133,558,451 86 LRP1B 2 140,986,740 87 LRP1B 2 142,371,550 88 LRP1B 2142,377,358 89 LRP1B 2 142,395,682 90 LRP1B 2 142,419,855 91 LRP1B 2142,598,638 92 KYNU 2 143,405,309 93 KYNU 2 143,455,211 94 KYNU 2143,516,377 95 KIF5C 2 149,600,091 96 CACNB4 2 152,587,594 97 CACNB4 2152,632,727 98 FMNL2 2 152,981,465 99 FMNL2 2 153,086,705 100 FMNL2 2153,096,733 101 FMNL2 2 153,097,194 102 FMNL2 2 153,146,684 103 FMNL2 2153,147,664 104 FMNL2 2 153,159,182 105 PKP4 2 159,240,155 106 PKP4 2159,240,805 107 SCN7A 2 166,998,337 108 CERKL 2 182,130,703 109 CERKL 2182,145,339 110 PDE1A 2 182,763,240 111 PARD3B 2 205,659,848 112 NRP2 2206,441,948 113 PIP5K3 2 208,956,492 114 DNER 2 229,932,713 115 CNTN6 31,414,974 116 CNTN4 3 2,326,831 117 CNTN4 3 2,395,095 118 CNTN4 32,476,259 119 CNTN4 3 2,509,772 120 ITPR1 3 4,688,162 121 ITPR1 34,715,592 122 IRAK2 3 10,234,114 123 ATP2B2 3 10,396,240 124 ATP2B2 310,411,869 125 SLC6A6 3 14,495,168 126 SLC6A6 3 14,495,564 127 DAZL 316,602,593 128 DAZL 3 16,611,541 129 ARPP-21 3 35,817,608 130 ARPP-21 335,819,665 131 STAC 3 36,433,107 132 STAC 3 36,445,311 133 ULK4 341,455,051 134 ULK4 3 41,476,741 135 ULK4 3 41,482,456 136 ULK4 341,501,971 137 ULK4 3 41,507,368 138 ZNF167 3 44,582,017 139 CACNA2D3 355,011,390 140 FLNB 3 58,093,595 141 FHIT 3 60,782,868 142 FHIT 361,135,266 143 FHIT 3 61,137,444 144 FHIT 3 61,146,142 145 FHIT 361,159,361 146 FHIT 3 61,182,117 147 FHIT 3 61,214,250 148 PRICKLE2 364,140,810 149 ADAMTS9 3 64,500,753 150 ADAMTS9 3 64,507,516 151 MAGI1 365,576,699 152 MAGI1 3 65,576,717 153 MAGI1 3 65,576,735 154 FOXP1 371,021,299 155 ROBO1 3 78,866,959 156 ROBO1 3 78,867,259 157 GBE1 381,669,129 158 GBE1 3 81,687,869 159 GBE1 3 81,859,450 160 EPHA6 398,268,377 161 CBLB 3 107,007,179 162 CBLB 3 107,007,333 163 PLCXD2 3112,949,845 164 PLCXD2 3 112,950,789 165 PLCXD2 3 112,953,907 166 PLCXD23 112,960,464 167 PLCXD2 3 112,964,847 168 EPHB1 3 136,129,897 169 SPSB43 142,287,637 170 SPSB4 3 142,294,879 171 SPSB4 3 142,328,274 172SERPINI2 3 168,658,115 173 SERPINI2 3 168,672,301 174 SERPINI2 3168,681,607 175 TNIK 3 172,402,113 176 PLD1 3 172,790,551 177 PLD1 3172,791,538 178 NLGN1 3 174,870,074 179 NLGN1 3 175,493,649 180 NLGN1 3175,515,979 181 NLGN1 3 175,543,000 182 LEPREL1 3 191,218,155 183LEPREL1 3 191,244,878 184 LEPREL1 3 191,245,227 185 LEPREL1 3191,250,258 186 LEPREL1 3 191,253,292 187 LEPREL1 3 191,261,577 188UBXD7 3 197,576,308 189 UBXD7 3 197,632,452 190 UBXD7 3 197,636,526 191SLC2A9 4 9,480,639 192 SLC2A9 4 9,502,295 193 SLC2A9 4 9,531,228 194LDB2 4 16,363,986 195 LDB2 4 16,365,914 196 KCNIP4 4 20,459,978 197STIM2 4 26,458,937 198 STIM2 4 26,459,024 199 STIM2 4 26,459,062 200STIM2 4 26,462,717 201 STIM2 4 26,462,750 202 STIM2 4 26,570,337 203KIAA1239 4 37,005,415 204 KIAA1239 4 37,007,192 205 UBE2K 4 39,464,805206 LIMCH1 4 41,213,350 207 LIMCH1 4 41,213,408 208 LIMCH1 4 41,221,506209 LIMCH1 4 41,223,320 210 LIMCH1 4 41,317,805 211 LOC389207 442,652,288 212 LOC389207 4 42,691,897 213 LOC389207 4 42,693,025 214SCD5 4 83,920,815 215 SCD5 4 83,923,596 216 HERC3 4 89,803,447 217 HERC34 89,843,208 218 FAM13A1 4 89,887,882 219 FAM13A1 4 89,915,913 220COL25A1 4 109,934,307 221 ANK2 4 114,340,609 222 CAMK2D 4 114,648,856223 NDST3 4 119,186,644 224 NDST3 4 119,256,090 225 GPR103 4 122,487,863226 MAML3 4 140,897,308 227 IL15 4 142,764,901 228 IL15 4 142,911,691229 IL15 4 142,924,868 230 INPP4B 4 143,414,201 231 INPP4B 4 143,421,104232 INPP4B 4 143,436,219 233 INPP4B 4 143,463,006 234 INPP4B 4143,524,042 235 INPP4B 4 143,547,226 236 INPP4B 4 143,566,886 237 INPP4B4 143,593,360 238 INPP4B 4 143,593,371 239 INPP4B 4 143,610,749 240POU4F2 4 147,739,219 241 POU4F2 4 147,758,283 242 DCLK2 4 151,378,402243 FSTL5 4 162,611,763 244 FSTL5 4 162,953,212 245 FSTL5 4 163,224,500246 TLL1 4 167,149,564 247 PALLD 4 169,939,539 248 PALLD 4 169,971,032249 CASP3 4 185,783,023 250 CASP3 4 185,791,294 251 PLEKHG4B 5 238,160252 PLEKHG4B 5 241,719 253 AHRR 5 401,598 254 AHRR 5 431,413 255 CTNND25 11,222,945 256 CTNND2 5 11,637,342 257 DNAH5 5 13,780,350 258 DNAH5 513,782,714 259 DNAH5 5 13,788,147 260 DNAH5 5 13,795,858 261 DNAH5 513,802,952 262 DNAH5 5 13,822,974 263 DNAH5 5 13,823,000 264 DNAH5 513,825,457 265 DNAH5 5 13,841,886 266 DNAH5 5 13,842,420 267 DNAH5 513,852,381 268 DNAH5 5 13,854,786 269 DNAH5 5 13,875,140 270 DNAH5 513,887,824 271 DNAH5 5 13,986,416 272 DNAH5 5 13,989,500 273 DNAH5 514,032,397 274 DNAH5 5 14,034,968 275 CDH10 5 24,728,325 276 CDH10 524,738,958 277 SLC45A2 5 33,979,974 278 SLC45A2 5 33,990,637 279 SLC1A35 36,670,315 280 SLC1A3 5 36,675,215 281 EGFLAM 5 38,269,319 282 EGFLAM5 38,296,060 283 EGFLAM 5 38,337,535 284 EGFLAM 5 38,357,424 285 EGFLAM5 38,382,422 286 EGFLAM 5 38,485,966 287 ITGA1 5 52,294,108 288 ITGA2 552,425,212 289 PDE4D 5 58,692,313 290 ELOVL7 5 60,152,959 291 ELOVL7 560,201,944 292 TNPO1 5 72,123,236 293 TNPO1 5 72,174,208 294 TNPO1 572,182,236 295 TNPO1 5 72,217,160 296 TNPO1 5 72,292,936 297 FCHO2 572,374,865 298 FCHO2 5 72,384,028 299 FCHO2 5 72,413,771 300 CMYA5 579,058,467 301 CMYA5 5 79,070,418 302 CMYA5 5 79,074,951 303 THBS4 579,376,918 304 THBS4 5 79,415,294 305 VCAN 5 82,914,275 306 MEF2C 588,138,619 307 GPR98 5 89,979,411 308 GPR98 5 89,986,028 309 GPR98 590,071,845 310 GPR98 5 90,428,377 311 FBXL17 5 107,223,636 312 FBXL17 5107,224,897 313 FBXL17 5 107,377,610 314 FBXL17 5 107,380,193 315 FBXL175 107,381,014 316 FBXL17 5 107,400,737 317 FBXL17 5 107,420,461 318FBXL17 5 107,556,166 319 FBXL17 5 107,612,678 320 PJA2 5 108,742,197 321PJA2 5 108,776,974 322 SNX2 5 122,116,630 323 SNX2 5 122,137,822 324SNX2 5 122,173,535 325 SNX2 5 122,174,171 326 SNX2 5 122,194,062 327SNX2 5 122,201,930 328 SNX24 5 122,232,671 329 SNX24 5 122,255,495 330SNX24 5 122,273,273 331 SNX24 5 122,283,900 332 SNX24 5 122,309,550 333SNX24 5 122,311,168 334 SNX24 5 122,383,127 335 ADAMTS19 5 129,039,887336 TRPC7 5 135,708,380 337 TRPC7 5 135,713,994 338 CTNNA1 5 138,167,176339 CTNNA1 5 138,264,654 340 CTNNA1 5 138,300,046 341 ODZ2 5 167,527,141342 ODZ2 5 167,606,948 343 ODZ2 5 167,621,874 344 ODZ2 5 167,634,311 345SERPINB6 6 2,876,878 346 SERPINB6 6 2,926,223 347 SLC22A23 6 3,395,265348 JARID2 6 15,537,710 349 JARID2 6 15,545,369 350 JARID2 6 15,624,264351 ATXN1 6 16,755,137 352 ATXN1 6 16,755,970 353 ATXN1 6 16,762,002 354RNF144B 6 18,526,687 355 RNF144B 6 18,530,528 356 RNF144B 6 18,553,561357 RNF144B 6 18,553,773 358 RNF144B 6 18,561,748 359 RNF144B 618,566,740 360 RNF144B 6 18,575,501 361 SLC17A4 6 25,876,893 362 SLC17A46 25,892,460 363 SLC17A1 6 25,917,888 364 SLC17A1 6 25,921,129 365SLC17A1 6 25,937,638 366 SLC17A1 6 25,939,191 367 SLC17A1 6 25,950,182368 SLC17A3 6 25,978,521 369 SLC17A2 6 26,067,106 370 BTN3A1 626,504,182 371 BTN3A1 6 26,513,969 372 BTN3A1 6 26,524,633 373 BTN2A3 626,532,708 374 BTN2A3 6 26,534,466 375 BTN3A3 6 26,553,839 376 BTNL2 632,463,841 377 BTNL2 6 32,482,600 378 LRFN2 6 40,528,210 379 ELOVL5 653,213,187 380 ELOVL5 6 53,221,300 381 ELOVL5 6 53,231,077 382 ELOVL5 653,238,040 383 ELOVL5 6 53,238,244 384 ELOVL5 6 53,242,957 385 ELOVL5 653,246,219 386 ELOVL5 6 53,254,362 387 ELOVL5 6 53,257,221 388 ELOVL5 653,257,463 389 ELOVL5 6 53,261,913 390 ELOVL5 6 53,262,169 391 ELOVL5 653,267,506 392 ELOVL5 6 53,271,049 393 ELOVL5 6 53,271,883 394 ELOVL5 653,280,718 395 ELOVL5 6 53,282,407 396 ELOVL5 6 53,284,867 397 ELOVL5 653,292,467 398 ELOVL5 6 53,294,567 399 ELOVL5 6 53,296,096 400 ELOVL5 653,298,093 401 ELOVL5 6 53,298,209 402 ELOVL5 6 53,314,948 403 ELOVL5 653,318,131 404 ELOVL5 6 53,341,053 405 ELOVL5 6 53,350,763 406 ELOVL5 653,362,070 407 ELOVL5 6 53,372,444 408 RIMS1 6 72,967,122 409 KLHL32 697,480,306 410 KLHL32 6 97,589,639 411 KLHL32 6 97,595,870 412 KLHL32 697,601,993 413 KLHL32 6 97,619,298 414 KLHL32 6 97,673,659 415 SLC22A166 110,900,563 416 SLC22A16 6 110,900,785 417 SLC22A16 6 110,903,098 418HS3ST5 6 114,502,447 419 TRDN 6 123,982,387 420 TRDN 6 123,991,308 421TRDN 6 124,017,012 422 NKAIN2 6 124,462,813 423 EYA4 6 133,642,955 424EYA4 6 133,643,088 425 EYA4 6 133,651,991 426 EYA4 6 133,861,896 427PDE7B 6 136,206,096 428 PDE7B 6 136,218,421 429 PDE7B 6 136,346,863 430PLAGL1 6 144,354,821 431 PLAGL1 6 144,355,380 432 UTRN 6 144,848,384 433SYNE1 6 152,510,881 434 SYNE1 6 152,511,829 435 SYNE1 6 152,553,368 436TFB1M 6 155,655,424 437 TFB1M 6 155,663,514 438 PARK2 6 161,941,630 439PARK2 6 161,952,077 440 PARK2 6 162,026,087 441 PDE10A 6 165,674,966 442PDE10A 6 165,679,905 443 SDK1 7 4,152,228 444 SDK1 7 4,153,102 445 SDK17 4,158,337 446 SDK1 7 4,162,572 447 NXPH1 7 8,590,239 448 NXPH1 78,633,152 449 NXPH1 7 8,633,615 450 SCIN 7 12,627,051 451 SCIN 712,634,312 452 DGKB 7 14,357,487 453 DGKB 7 14,357,894 454 DGKB 714,471,463 455 DGKB 7 14,472,219 456 DGKB 7 14,529,482 457 DGKB 714,539,481 458 FERD3L 7 19,167,340 459 STK31 7 23,760,554 460 SKAP2 726,770,543 461 SKAP2 7 26,795,178 462 SKAP2 7 26,814,684 463 SKAP2 726,827,213 464 SKAP2 7 26,830,698 465 SKAP2 7 26,858,965 466 SKAP2 726,880,921 467 CREB5 7 28,811,671 468 CREB5 7 28,906,935 469 CREB5 728,953,482 470 CHN2 7 29,215,509 471 PDE1C 7 32,037,670 472 PDE1C 732,064,508 473 PDE1C 7 32,141,959 474 BMPER 7 34,112,924 475 BMPER 734,176,289 476 BMPER 7 34,184,882 477 EEPD1 7 36,280,985 478 EEPD1 736,391,476 479 VPS41 7 38,798,875 480 VPS41 7 38,806,116 481 VPS41 738,812,386 482 VPS41 7 38,859,847 483 VPS41 7 38,908,142 484 VPS41 738,911,555 485 VPS41 7 38,936,691 486 CDC2L5 7 40,063,896 487 ABCA13 748,363,317 488 ABCA13 7 48,380,185 489 ABCA13 7 48,427,057 490 ABCA13 748,454,811 491 ABCA13 7 48,714,222 492 GRB10 7 50,823,341 493 GRB10 750,848,124 494 WBSCR17 7 70,313,808 495 WBSCR17 7 70,765,881 496 CALN1 771,180,137 497 CALN1 7 71,235,264 498 CALN1 7 71,338,388 499 CALN1 771,339,231 500 CALN1 7 71,344,745 501 MAGI2 7 77,856,639 502 MAGI2 777,950,934 503 MAGI2 7 78,091,049 504 MAGI2 7 78,305,682 505 MAGI2 778,554,879 506 MAGI2 7 78,581,862 507 MAGI2 7 78,589,166 508 MAGI2 778,760,470 509 MAGI2 7 78,817,962 510 SEMA3E 7 83,011,138 511 ABCB4 786,897,339 512 GTPBP10 7 89,357,529 513 PPP1R9A 7 94,401,225 514 PPP1R9A7 94,411,224 515 PPP1R9A 7 94,431,076 516 PPP1R9A 7 94,479,997 517PPP1R9A 7 94,534,075 518 PPP1R9A 7 94,589,831 519 PPP1R9A 7 94,632,721520 PPP1R9A 7 94,677,380 521 PPP1R9A 7 94,681,040 522 PPP1R9A 794,717,161 523 PPP1R9A 7 94,733,892 524 PPP1R9A 7 94,747,598 525 PPP1R9A7 94,748,184 526 DYNC1I1 7 95,556,260 527 ZNF3 7 99,480,681 528 ZNF3 799,516,558 529 NRCAM 7 107,585,096 530 NRCAM 7 107,598,816 531 NRCAM 7107,608,956 532 NRCAM 7 107,618,181 533 NRCAM 7 107,621,970 534 NRCAM 7107,626,668 535 NRCAM 7 107,627,184 536 NRCAM 7 107,628,207 537 NRCAM 7107,738,458 538 NRCAM 7 107,862,002 539 KCND2 7 119,925,320 540 KCND2 7119,999,690 541 KCND2 7 120,001,113 542 KCND2 7 120,018,452 543 CADPS2 7122,066,038 544 CADPS2 7 122,074,175 545 CADPS2 7 122,146,928 546SLC13A1 7 122,533,104 547 SLC13A1 7 122,560,268 548 SLC13A1 7122,596,470 549 SLC13A1 7 122,633,763 550 SLC13A1 7 122,659,570 551 GRM87 125,938,463 552 GRM8 7 125,940,799 553 GRM8 7 125,974,975 554 GRM8 7126,100,080 555 GRM8 7 126,134,129 556 GRM8 7 126,159,625 557 GRM8 7126,165,491 558 GRM8 7 126,174,101 559 GRM8 7 126,208,986 560 GRM8 7126,225,935 561 GRM8 7 126,234,800 562 GRM8 7 126,436,133 563 GRM8 7126,483,848 564 GRM8 7 126,674,369 565 GRM8 7 126,692,493 566 EXOC4 7132,728,495 567 EXOC4 7 132,754,657 568 EXOC4 7 132,756,739 569 EXOC4 7132,889,141 570 EXOC4 7 133,264,961 571 DGKI 7 136,723,471 572 DGKI 7136,749,535 573 DGKI 7 136,769,973 574 DGKI 7 136,775,455 575 DGKI 7136,780,737 576 DGKI 7 136,838,221 577 DGKI 7 136,925,970 578 TBXAS1 7139,184,991 579 CNTNAP2 7 145,414,794 580 CNTNAP2 7 145,900,444 581CNTNAP2 7 146,180,657 582 CNTNAP2 7 146,405,829 583 CNTNAP2 7146,414,565 584 CNTNAP2 7 146,788,354 585 CNTNAP2 7 146,792,712 586CNTNAP2 7 146,795,212 587 CNTNAP2 7 147,069,599 588 CNTNAP2 7147,073,223 589 CNTNAP2 7 147,710,739 590 PTPRN2 7 157,017,352 591PTPRN2 7 157,020,289 592 PTPRN2 7 157,499,807 593 PTPRN2 7 157,634,704594 PTPRN2 7 157,676,114 595 PTPRN2 7 157,714,280 596 PTPRN2 7158,015,477 597 CSMD1 8 2,793,553 598 CSMD1 8 2,864,416 599 CSMD1 82,943,570 600 CSMD1 8 2,954,259 601 CSMD1 8 3,228,881 602 CSMD1 83,230,805 603 CSMD1 8 3,232,022 604 CSMD1 8 3,232,222 605 CSMD1 83,245,103 606 CSMD1 8 3,250,935 607 CSMD1 8 3,338,555 608 MCPH1 86,414,463 609 MCPH1 8 6,488,786 610 SGCZ 8 14,619,388 611 SLC7A2 817,436,984 612 SLC7A2 8 17,444,141 613 PSD3 8 18,428,754 614 PSD3 818,431,654 615 PSD3 8 18,440,935 616 PSD3 8 18,457,737 617 PSD3 818,465,235 618 PSD3 8 18,467,749 619 PSD3 8 18,469,732 620 PSD3 818,514,979 621 PSD3 8 18,558,380 622 PSD3 8 18,736,236 623 PSD3 818,749,712 624 PSD3 8 18,750,003 625 PSD3 8 18,819,182 626 PSD3 818,953,685 627 ENTPD4 8 23,357,109 628 UNC5D 8 35,516,694 629 SNTG1 851,805,005 630 SNTG1 8 51,816,608 631 LYN 8 57,039,314 632 LYN 857,053,118 633 LYN 8 57,054,784 634 LYN 8 57,108,529 635 LYN 857,110,114 636 PLAG1 8 57,246,679 637 PLAG1 8 57,263,345 638 TOX 859,966,273 639 TOX 8 59,972,497 640 TOX 8 59,980,027 641 TOX 860,198,077 642 NKAIN3 8 63,649,765 643 NKAIN3 8 63,900,353 644 NKAIN3 863,935,531 645 NKAIN3 8 63,936,341 646 DEPDC2 8 69,208,963 647 DEPDC2 869,209,296 648 CRISPLD1 8 76,073,693 649 CRISPLD1 8 76,086,655 650CRISPLD1 8 76,127,254 651 CRISPLD1 8 76,156,200 652 CRISPLD1 876,158,048 653 MMP16 8 89,276,696 654 BAALC 8 104,271,601 655 ZFPM2 8106,614,970 656 ZFPM2 8 106,687,838 657 ZFPM2 8 106,688,431 658 ZFPM2 8106,847,240 659 ZFPM2 8 106,880,874 660 CSMD3 8 113,337,274 661 CSMD3 8113,443,580 662 CSMD3 8 113,452,239 663 CSMD3 8 113,467,267 664 CSMD3 8113,469,659 665 CSMD3 8 113,473,493 666 CSMD3 8 113,510,014 667 CSMD3 8113,554,821 668 CSMD3 8 114,069,034 669 CSMD3 8 114,093,751 670 CSMD3 8114,098,597 671 CSMD3 8 114,104,594 672 CSMD3 8 114,105,767 673 CSMD3 8114,160,908 674 CSMD3 8 114,208,773 675 CSMD3 8 114,359,208 676 SAMD12 8119,514,190 677 SAMD12 8 119,514,541 678 SAMD12 8 119,518,606 679 SAMD128 119,531,636 680 SAMD12 8 119,587,094 681 SAMD12 8 119,680,657 682SAMD12 8 119,719,731 683 FER1L6 8 125,053,616 684 FER1L6 8 125,122,813685 FER1L6 8 125,123,546 686 MTSS1 8 125,634,509 687 MTSS1 8 125,700,325688 MTSS1 8 125,708,636 689 MTSS1 8 125,737,780 690 MTSS1 8 125,802,038691 DDEF1 8 131,286,874 692 DDEF1 8 131,298,362 693 DDEF1 8 131,368,653694 DDEF1 8 131,406,218 695 DDEF1 8 131,423,273 696 KCNQ3 8 133,208,937697 KCNQ3 8 133,211,492 698 KCNQ3 8 133,212,327 699 KCNQ3 8 133,346,913700 KCNQ3 8 133,351,663 701 COL22A1 8 139,744,740 702 COL22A1 8139,759,058 703 COL22A1 8 139,771,875 704 COL22A1 8 139,777,590 705COL22A1 8 139,833,578 706 ZC3H3 8 144,691,326 707 SMARCA2 9 2,053,356708 SMARCA2 9 2,170,694 709 PIP5K1B 9 70,545,037 710 PIP5K1B 970,687,329 711 TRPM3 9 72,616,673 712 TMC1 9 74,485,413 713 TMC1 974,492,549 714 TMC1 9 74,493,473 715 TMC1 9 74,507,694 716 TMC1 974,623,740 717 PCSK5 9 77,897,682 718 GNAQ 9 79,856,574 719 GNAQ 979,934,142 720 GNAQ 9 79,946,188 721 NTRK2 9 86,577,727 722 DIRAS2 992,422,258 723 DIRAS2 9 92,476,677 724 NFIL3 9 93,218,808 725 FKTN 9107,389,052 726 FKTN 9 107,409,195 727 FKTN 9 107,420,176 728 FKTN 9107,435,753 729 FKTN 9 107,445,165 730 FKTN 9 107,449,221 731 FKTN 9107,449,435 732 PALM2 9 111,506,598 733 PALM2 9 111,552,543 734 PALM2 9111,554,864 735 PALM2 9 111,555,049 736 PALM2 9 111,556,167 737 ZNF618 9115,804,104 738 ZNF618 9 115,816,110 739 ZNF618 9 115,820,286 740 ASTN29 119,198,404 741 CDK5RAP2 9 122,346,776 742 CDK5RAP2 9 122,377,819 743PTGS1 9 124,225,832 744 RALGPS1 9 128,769,224 745 RALGPS1 9 128,809,594746 RALGPS1 9 128,850,765 747 RALGPS1 9 128,902,817 748 RALGPS1 9128,972,837 749 SLC25A25 9 129,899,153 750 TSC1 9 134,778,093 751 TSC1 9134,786,003 752 TSC1 9 134,812,111 753 VAV2 9 135,708,866 754 VAV2 9135,710,406 755 VAV2 9 135,710,620 756 VAV2 9 135,714,835 757 PITRM1 103,179,115 758 PRKCQ 10 7,131,891 759 PRKCQ 10 7,136,154 760 PRKCQ 107,137,198 761 CACNB2 10 18,861,080 762 ARMC3 10 23,264,868 763 ARMC3 1023,270,471 764 ARMC3 10 23,271,006 765 ARMC3 10 23,343,259 766 ARMC3 1023,343,422 767 ARMC3 10 23,372,821 768 ARMC3 10 23,372,952 769 MYO3A 1026,396,941 770 MYO3A 10 26,412,733 771 ANK3 10 61,569,339 772 JMJD1C 1064,732,014 773 JMJD1C 10 64,736,192 774 JMJD1C 10 64,791,571 775 JMJD1C10 64,873,814 776 CDH23 10 72,997,429 777 KCNMA1 10 78,258,751 778KCNMA1 10 78,320,267 779 SORCS3 10 106,525,169 780 VTI1A 10 114,448,959781 VTI1A 10 114,458,127 782 VTI1A 10 114,496,282 783 VTI1A 10114,497,586 784 VTI1A 10 114,504,041 785 ATRNL1 10 117,429,854 786HSPA12A 10 118,432,901 787 GRK5 10 121,055,451 788 ATE1 10 123,478,029789 ATE1 10 123,484,634 790 ATE1 10 123,634,335 791 ATE1 10 123,644,015792 ATE1 10 123,648,119 793 ATE1 10 123,648,218 794 ATE1 10 123,648,608795 ATE1 10 123,666,737 796 ATE1 10 123,669,674 797 ATE1 10 123,679,356798 STIM1 11 4,033,624 799 STIM1 11 4,047,324 800 TRIM21 11 4,371,449801 GALNTL4 11 11,222,747 802 GALNTL4 11 11,228,193 803 GALNTL4 1111,246,740 804 SPON1 11 13,883,488 805 SPON1 11 14,244,704 806 USH1C 1117,475,101 807 USH1C 11 17,487,060 808 USH1C 11 17,489,173 809 USH1C 1117,489,973 810 USH1C 11 17,490,211 811 USH1C 11 17,491,427 812 USH1C 1117,519,298 813 USH1C 11 17,520,065 814 USH1C 11 17,523,687 815 IGSF22 1118,689,422 816 IGSF22 11 18,692,523 817 IGSF22 11 18,694,857 818C11ORF49 11 46,955,088 819 C11ORF49 11 47,130,872 820 C11ORF49 1147,132,581 821 DLG2 11 82,843,293 822 DLG2 11 82,856,041 823 DLG2 1182,910,180 824 DLG2 11 83,186,640 825 DLG2 11 83,187,421 826 DLG2 1183,203,872 827 DLG2 11 83,366,230 828 DLG2 11 84,153,124 829 DLG2 1184,175,263 830 DLG2 11 84,198,828 831 DLG2 11 84,234,326 832 ELMOD1 11107,051,899 833 OPCML 11 131,718,194 834 TSPAN9 12 3,058,775 835 TSPAN912 3,065,463 836 TSPAN9 12 3,173,346 837 TSPAN9 12 3,331,863 838 STYK112 10,666,462 839 STYK1 12 10,697,767 840 STYK1 12 10,708,924 841 STYK112 10,711,189 842 LOC729025 12 16,250,464 843 LRP1 12 55,847,718 844LRP1 12 55,878,824 845 CNOT2 12 68,831,198 846 CNOT2 12 69,026,461 847KCNC2 12 73,584,602 848 NAV3 12 76,913,545 849 NAV3 12 76,922,312 850GAS2L3 12 99,519,980 851 MTIF3 13 26,895,700 852 MTIF3 13 26,895,999 853SLC46A3 13 28,185,843 854 SLC46A3 13 28,217,711 855 SLC46A3 1328,267,317 856 UBL3 13 29,194,621 857 N4BP2L2 13 32,021,516 858 NBEA 1335,086,809 859 NBEA 13 35,087,894 860 NBEA 13 35,130,015 861 SLAIN1 1377,151,328 862 GPC5 13 91,268,794 863 GPC5 13 91,346,842 864 GPC5 1391,372,652 865 GPC6 13 93,138,384 866 GPC6 13 93,183,430 867 NALCN 13100,517,778 868 NALCN 13 100,522,814 869 ITGBL1 13 101,013,965 870 WDR2314 23,657,479 871 WDR23 14 23,671,158 872 NPAS3 14 32,590,670 873 NPAS314 32,658,581 874 GNG2 14 51,414,961 875 GNG2 14 51,422,662 876 SAMD4A14 54,319,095 877 SAMD4A 14 54,335,279 878 SAMD4A 14 54,335,321 879PPP2R5E 14 63,040,607 880 PPP2R5E 14 63,099,534 881 RGS6 14 71,538,177882 RGS6 14 71,539,344 883 RGS6 14 71,540,089 884 RGS6 14 71,723,690 885RGS6 14 71,793,717 886 KCNK10 14 87,792,199 887 KCNK13 14 89,783,756 888KCNK13 14 89,785,725 889 PSMC1 14 89,794,414 890 PSMC1 14 89,794,847 891PSMC1 14 89,806,078 892 RPS6KA5 14 90,412,434 893 RPS6KA5 14 90,501,524894 RPS6KA5 14 90,527,909 895 RPS6KA5 14 90,557,351 896 RPS6KA5 1490,572,871 897 RPS6KA5 14 90,600,927 898 RPS6KA5 14 90,616,889 899CCDC88C 14 90,821,027 900 CCDC88C 14 90,910,783 901 CCDC88C 1490,916,433 902 CCDC88C 14 90,918,598 903 CCDC88C 14 90,920,049 904BCL11B 14 98,746,376 905 BCL11B 14 98,757,526 906 BCL11B 14 98,765,857907 ATP10A 15 23,493,398 908 ATP10A 15 23,513,966 909 C15ORF41 1534,833,829 910 GLDN 15 49,457,768 911 GLDN 15 49,457,862 912 GLDN 1549,459,928 913 GLDN 15 49,460,922 914 CLK3 15 72,707,585 915 CLK3 1572,727,323 916 TBC1D2B 15 76,083,890 917 TBC1D2B 15 76,098,398 918 PCSK615 99,842,741 919 PCSK6 15 99,858,640 920 A2BP1 16 7,444,597 921 A2BP116 7,547,113 922 A2BP1 16 7,568,164 923 TMC5 16 19,365,820 924 TMC5 1619,403,812 925 TMC5 16 19,413,252 926 TMC5 16 19,432,372 927 GDE1 1619,435,278 928 GDE1 16 19,455,004 929 HYDIN 16 69,765,380 930 HYDIN 1669,818,152 931 HYDIN 16 69,856,735 932 WWOX 16 76,673,124 933 WWOX 1676,739,487 934 WWOX 16 76,793,572 935 WWOX 16 77,041,675 936 MPHOSPH6 1680,728,868 937 MPHOSPH6 16 80,759,877 938 MPHOSPH6 16 80,765,783 939MPHOSPH6 16 80,777,144 940 MPHOSPH6 16 80,817,367 941 MPHOSPH6 1680,820,057 942 MPHOSPH6 16 80,831,708 943 MPHOSPH6 16 80,833,378 944CDH13 16 81,390,450 945 CDH13 16 81,430,291 946 CDH13 16 82,324,245 947USP10 16 83,325,736 948 DNAH9 17 11,643,618 949 DNAH9 17 11,671,648 950RAB11FIP4 17 26,746,745 951 CA10 17 47,069,220 952 CA10 17 47,599,744953 HRNBP3 17 74,845,144 954 ZFP161 18 5,280,198 955 ZFP161 18 5,283,943956 ZFP161 18 5,284,323 957 ZFP161 18 5,398,814 958 ZFP161 18 5,406,160959 PTPRM 18 7,585,927 960 PTPRM 18 7,892,147 961 PTPRM 18 8,041,285 962KIAA0802 18 8,840,062 963 KIAA0802 18 8,844,132 964 OSBPL1A 1820,105,278 965 CHST9 18 22,787,798 966 CHST9 18 22,874,298 967 CHST9 1822,874,628 968 CHST9 18 23,010,213 969 CHST9 18 23,012,354 970 NEDD4L 1854,173,333 971 NEDD4L 18 54,202,587 972 NEDD4L 18 54,258,677 973 NEDD4L18 54,259,246 974 CCBE1 18 55,220,303 975 CCBE1 18 55,241,702 976 CCBE118 55,483,138 977 CDH7 18 61,594,009 978 CDH7 18 61,697,973 979 CDH7 1861,739,825 980 CDH7 18 61,759,477 981 TXNDC10 18 64,536,945 982 ATRN 203,400,447 983 FERMT1 20 6,037,513 984 FERMT1 20 6,041,177 985 PLCB1 208,000,158 986 PLCB4 20 9,433,807 987 MACROD2 20 15,551,153 988 MACROD220 15,559,316 989 MACROD2 20 15,586,912 990 MACROD2 20 16,020,951 991KIF16B 20 16,445,469 992 KIF16B 20 16,454,369 993 MAPRE1 20 30,888,730994 MAPRE1 20 30,906,484 995 PTPRT 20 40,087,340 996 ZSWIM3 2043,921,606 997 ZSWIM3 20 43,930,226 998 ZSWIM3 20 43,939,825 999 SNAI120 48,025,165 1000 SNAI1 20 48,036,030 1001 SNAI1 20 48,037,294 1002SNAI1 20 48,051,852 1003 BMP7 20 55,238,534 1004 CDH4 20 59,359,672 1005C21ORF37 21 17,711,037 1006 C21ORF37 21 17,738,145 1007 NCAM2 2121,399,144 1008 NCAM2 21 21,451,606 1009 NCAM2 21 21,658,511 1010 NCAM221 21,664,277 1011 PDE9A 21 43,061,181 1012 ARVCF 22 18,342,203 1013ARVCF 22 18,371,950 1014 SGSM1 22 23,675,537 1015 ASPHD2 22 25,130,1991016 ASPHD2 22 25,131,287 1017 ASPHD2 22 25,166,780 1018 HPS4 2225,200,502 1019 ARFGAP3 22 41,536,894 1020 ARFGAP3 22 41,576,090 1021TTLL1 22 41,789,790 1022 TTLL1 22 41,822,906 1023 EFCAB6 22 42,411,0131024 EFCAB6 22 42,527,300 1025 RIBC2 22 44,217,310

1. A method of determining risk of developing schizophrenia (SZ) in ahuman subject, the method comprising: determining the identity of atleast one allele of a single nucleotide polymorphism (SNP) listed inTable 1; and comparing the identity of the allele in the subject with areference allele, wherein the reference allele is associated with aknown risk of developing SZ; and wherein the presence of an allele inthe subject that is the same as the reference allele that is associatedwith the known risk of developing SZ indicates the risk that the subjectwill develop SZ.
 2. A method of determining risk of developing SZ in ahuman subject, the method comprising: determining the copy number of atleast one single nucleotide polymorphism (SNP) listed in Table 2 or 3;and comparing the copy number of the SNP in the subject with a referencecopy number, wherein the reference copy number is associated with aknown risk of developing SZ; and wherein the presence of a copy numberof the SNP in the subject that is the same as a reference copy numberthat is associated with SZ indicates that the risk that the subject willdevelop SZ.
 3. The method of claim 1 or 2, wherein determining theidentity or copy number of an allele comprises obtaining a samplecomprising DNA from the subject, and determining identity or copy numberof the nucleotide at the polymorphic site.
 4. The method of claim 3,wherein determining the identity of the nucleotide comprises contactingthe sample with a probe specific for a selected allele of thepolymorphism, and detecting the formation of complexes between the probeand the selected allele of the polymorphism, wherein the formation ofcomplexes between the probe and the test marker indicates the presenceof the selected allele in the sample.
 5. The method of claim 4, whereindetermining the identity of an allele comprises determining the identityof the nucleotide at position 31 of one of SEQ ID NOs: 1-1025.
 6. Themethod of claim 3, wherein determining the copy number of an allelecomprises contacting the sample with a probe specific for a selectedallele, detecting the formation of complexes between the probe and theselected allele of the polymorphism, and quantifying the complexes,wherein the quantification of the complexes indicates the copy number ofthe selected allele in the sample.
 7. The method of claim 6, wherein theprobe comprises a fluorescent label, and quantifying the complexescomprises detecting intensity of emission from the label.
 8. The methodof claim 2, wherein determining the copy number of an allele comprisesdetecting the absence or duplication of the allele in the subject. 9.The method of claim 1 or 2, wherein the subject is a patient having orsuspected of having SZ.
 10. The method of claim 1 or 2, wherein thesubject has one or more risk factors associated with SZ.
 11. The methodof claim 8, wherein the risk factors associated with SZ include one ormore of: a relative afflicted with SZ; and a genetically basedphenotypic trait associated with risk for a SZ.
 12. The method of claim1 or 2, wherein the subject has exhibited or exhibits symptoms ofpsychosis.
 13. The method of claim 1 or 2, further comprising selectingor excluding a subject for enrollment in a clinical trial based on theidentity of the allele.
 14. The method of claim 1 or 2, furthercomprising stratifying a subject population for analysis of a clinicaltrial based on the identity of the allele in the subjects.
 15. Themethod of claim 1 or 2, further comprising confirming a diagnosis of aSZ using psychometric instruments.
 16. The method of claim 1, furthercomprising selecting a treatment for SZ if an allele in the subject isthe same as a reference allele associated with SZ.
 17. The method ofclaim 2, further comprising selecting a treatment for SZ if the copynumber of the allele in the subject is the same as a reference copynumber associated with SZ.
 18. The method of claim 14 or 15, furthercomprising administering the selected treatment to the subject.
 19. Themethod of claim 14 or 15, wherein the treatment comprises one or more ofan anti-psychotic drug, an anti-depressant drug, anti-anxiety drug, moodstabilizer, selective serotonin reuptake inhibitor (SSRI),psychotherapy, or a stimulant.
 20. The method of claim 1 or 2, furthercomprising recording the identity of the allele in a tangible medium.21. The method of claim 1 or 2, wherein the tangible medium comprises acomputer-readable disk, a solid state memory device, or an opticalstorage device.
 22. The method of claim 1, wherein the single nucleotidepolymorphism (SNP) is at position 31 of a sequence selected from thegroup consisting of SEQ ID NO:656, 665, 248, 639, 25, 494, 700, and 691.23. The method of claim 2, wherein the single nucleotide polymorphism(SNP) is at position 31 of a sequence selected from the group consistingof SEQ ID NO:665, 314, 679, 597, 523, 619, 402, 677, 586, 558, 664, 87,851, and 500.